Gut, 1975, 16, 298-329

Symposium on colonic function1Electrophysiology of the colon

E. E. DANIEL

From the Department ofPharmacology, The University ofAlberta, Edmonton, Canada

One approach to an analysis of the electrophysiologyof smooth muscle and nerves of the large bowel isto examine small bits of them as examples of smoothmuscle tissues, without any consideration of thefunctions of the whole organ. Another approach,more relevant to clinical problems, involves analysisof how the components of the organ are controlledand integrated to form a functional unit. The largebowel transfers the semiliquid contents it receivesfrom the ileum to the rectum in such a way as toallow for extraction of electrolytes and water andfor other changes in composition en route. Sinceevacuation of contents from the rectum is usuallya periodic phenomenon, and input by evacuationfrom the ileum is probably also periodic, there mustbe coupling in some way between input and output;and there must also be a system of controls toprovide for orderly delays and movements of thecolonic contents during transit.To understand the control system for transit in the

large bowel, a systematic approach seems warranted.I believe one should begin with an analysis of therange of responses which its muscle components canexecute (Daniel, 1973). This requires considerationof the origin and integration of spontaneouselectrical and mechanical activity of the musculatureof the large bowel during normal and abnormalmotor activity. A question soon arises: Whichresponses are initiated and integrated by the smoothmuscle alone? Answering this question leads tocharacterization of the properties of the myogeniccontrol system. If complete, this characterizationwould provide information about the cellularelectrical activities, cell-to-cell coupling in musclelayers and coupling between layers, and the trans-lation of these activities into mechanical responses.A number of gastrointestinal myogenic control

systems, particularly of stomach and small bowel(see Daniel, 1973; Sarna, Daniel, and Kingma,1971, 1972a, b, and c), have been characterized asmyogenic systems of mutually coupled relaxation'The following five papers (pp 298-329) were given at the springmeeting 1974 of the British Society of Gastroenterology.

oscillators. These systems are integrated in time andspace within the longitudinal muscle layer by havingthe highest frequency oscillator proximal (in relationto the direction of net transit) and by having appro-priate coupling so that distal lower frequencyoscillators are pulled up or phase locked (fig 1).This leads either to higher frequency of contraction

A

B1

B2

Phase Lag

D

Phase Lag

Fig 1 Effect of increasing coupling on oscillationfrequencies of two bowel oscillators. In A, proximal one(top) is shown to have a higher uncoupled (intrinsic)frequency than a distal one (bottom). As the extent ofmutual coupling (fraction of the output of one whichreaches the input of the other) is increased, thefrequency of the lower frequency oscillator can bepulled up (B1), that of the lower frequency oscillatorcan be pulled down (B2), or both changes can occur(not shown). With sufficient coupling, the oscillatorsbecome phase-locked (C and D); the greater thecoupling, the less the phase lag between them (D).

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proximally, or to an appropriate phase lead byproximal over distal regions of muscle. Around thecircumference, the coupling is tight so that oscilla-tions of excitability occur nearly simultaneously.

This system of coupled electrical oscillations leadsto control' in time and space of the excitability ofgastrointestinal smooth muscle organs. However, thetranslation of this excitability into contraction seemsusually to be a function of neurogenic and hormonalcontrol or modulation mechanisms.There is strong evidence for the existence of such

systems of coupled relaxation oscillators in the non-fundal portions of the stomach, in the small intes-tine, and in the large bowel of the cat (see Sarna etal, 1971, 1972a, b, and c; Daniel, 1973; and below).In stomach and intestine, oscillatory controlpotentials originate in the longitudinal muscle andspread into the circular muscle; in the cat colon withnquronal modulation, they originate in circularmuscle.There is a marked contrast between the above

hypothesis of a basic control system, dependent onmyogenic activity and integration through modulationby nerves and hormones, and the traditional hypo-thesis of control via an intricate network of nervepathways for integrated responses such as the peri-staltic reflex.One aspect of the peristaltic reflex model of

control of motor function in the gut has been widelyaccepted for many systems; ie, distal inhibition inresponse to stretch and to pharmacological andelectrical stimuli. There may be tonic activity in sucha system. This distal inhibitory response seems to bemediated by an intrinsic neuronal system-non-adrenergic inhibitory nerves (Burnstock, 1972).

These two models are not mutually exclusive,though one or the other may be more applicable toone git region or to one species. I shall emphasizethe model of myogenic control, because it is not yetwidely known.

Anatomy of the Large Bowel

The anatomy ofany system provides basic constraintson the nature of any control systems which operate.There can be no control without communicationbetween elements of the system; eg, nerves cannotcontrol muscles unless they have endings sufficientlyclose to allow chemical communication to occur.Also, one muscle cannot pace another without themeans to communicate a signal to it. There is

'For this reason we refer to the oscillatory potentials as controlpotentials. These potentials are also known descriptively as slow waves,pacemaker potentials, BER, etc. The term 'control potentials' shouldnot be used for these potentials unless they do in fact control theintegration of motility.

299

surprisingly little information about the structure ofthe basic myogenic system, ie, the nature of pathwaysof electrical or chemical communications (the cell-to-cell contacts) have not been studied within musclelayers or in different regions of the large bowel, norhave arrangements for communication betweenmuscle layers been agreed upon (Elsen and Arey,1966; Pace, 1967; Schofield, 1968; and Pace andWilliams, 1969). Substructure within the circularmuscle layer of human colon has been examined in apreliminary way (Pace and Williams, 1969), with thesuggestion that there are bands about 1 mm widedivided by transverse septa; within these bands, thereare reported to be further subdivisions into fasciculi.The longitudinal muscle is a continuous layer,thickened at the three taenia which are in turnpartially subdivided by incomplete grooves runningin their long axes. The connexions between taeniaand circular muscle are quite controversial. The lcciof nerves in human colon in limited studies seemfairly typical of the rest of the gut (Schofield, 1968):preganglionic cholinergic as well as postganglionicadrenergic fibres synapsing on postganglioniccholinergic ganglia, dendrites and axons in themyenteric and submucous plexuses (Gannon,Noblet, and Burnstock, 1969; Garrett, Howard, andNixon, 1969). There are also non-adrenergicinhibitory ganglia in the plexuses. The extrinsic andintrinsic connexions of non-adrenergic inhibitoryfibres are unknown.

There are two basic anatomical patterns in thelarge bowels of different species. One is characteristicof herbivores such as rabbits and guinea pigs: alarge proximal part is sacculated with the longitudinalmuscle partially absent. The remainder of the colonis narrower, devoid of sacculation, and has auniform muscle coat. In omnivores like the cat anddog, the colon is short, without sacculations, with auniform longitudinal muscle coat and a vestigialcaecum. Man, an omnivore, is in between closerto herbivores in structure. In the species in whichmyogenic control systems have been most extensivelyanalysed (the cat colon) there are no taenia; instead,the longitudinal muscle is everywhere a uniform,continuous coat. Howard and Garrett (1973) havepointed out that in the cat there are direct adrenergicfibres innervating longitudinal muscle in distalcolon and rectum, and circular muscle in lowerrectum and internal sphincter. In colon, the sameneurone organization as in the human seems to exist,except for the direct adrenergic fibres to muscle.Whether this arrangement of muscles and nerves isstructurally and functionally equivalent to thehuman system with its taenia is unknown; so studiesfrom cat colon cannot yet be extrapolated to thehuman large bowel.

E. E. Daniel

Cat Human Guinea Pig

LM CM LM CM LM CM

Parasympathetic and/oracetylcholine t t t t t t

Sympathetic and/ornoradrenaline2

Nonadrenergicinhibitory ? ? ? ?

Table I Responses to nerve mediators'ISee Heulten (1969), Wienbeck and Christensen (1971a), Bucknell andWhitney (1964), Bennett and Whitney (1966), Belisle and Gagnon(1971), Burnstock (1972).2Low doses of noradrenaline or higher doses in the presence of a9-adrenergic antagonist may cause contractile responses in the cat orhuman.

How activity of the various colonic nerves modu-lates the electrical and contractile responses issummarized in table I. Thus vagal and sacral nerveactivity would activate colonic response potentialsand motility either directly or by coupling of re-sponse spikes to control potentials; and sympatheticnerve activity might relax or uncouple contractionsby inhibiting acetylcholine release or by actingdirectly to inhibit muscle. Stimulation or tonicactivity of nonadrenergic neurones could inhibitmuscle contraction directly.'

Cat Colon

MYOGENIC CONTROL SYSTEMTwo electrical control systems for the colon will bediscussed: that of the cat has been most extensivelyanalysed; it may or may not be similar to that ofman.

'There is evidence suggesting that in the myogenic system contractionwould normally be coupled to control potentials but for the tonicactivity of inhibitory nerves. Though multiple neurological derange-ments occur in aganglionosis of the large bowel (loss of intrinsiccholinergic and of intrinsic nonadrenergic inhibitory ganglia as wellas of sensory cell bodies, plus overgrowth of extrinsic nerves), thefundamental defect may be loss of tonic inhibitory control.

Nature and origin of control waves (slow waves)Christensen and colleagues showed that the cat colonin vitro showed the characteristics of coupled relaxa-tion oscillators. The circular muscle generates slowwaves, which are periodic depolarizations andrepolarizations when recorded with microelectrodes(figure 2a, b). They can easily oe recorded by simpleglass-pore as well as by other types of electrode(fig 2) in preparations from which the mucosa hasbeen stripped. Slow waves so recorded are controlwaves in the sense that when action potential spikesand contractions occur under the influence ofcholinergic and other drugs, they occur in burstsphase-locked to the slow potentials; and the durationof the slow wave increases (fig 3). However, itshould be noted that slow waves recorded withmicroelectrodes show few superimposed spikes.Some spikes recorded with extracellular electrodesmay originate in longitudinal muscle.

Circular muscle cells throughout the cat colon arecapable of generating control potentials. The size ofthe unit generating oscillations is unknown, but it isless than 4 mm probably less than 0-5 mm, andmaybe as small as a single cell (Christensen andRasmus, 1972).When isolated colon circular muscle was cut into

2-cm rings (Christensen, Anuras, and Hauser, 1974),there was a gradient of intrinsic frequencies increas-ing distally (fig 4). When intact and electricallycoupled, the proximal oscillators were pulled up infrequency by the higher frequency distal one, and thedistal oscillators were pulled down slightly. As aconsequence of the characteristics of coupled relaxa-tion oscillators, distal oscillators (especially inproximal colon) contracted more frequently, and inphase-locked regions usually had phase lead overproximal ones (Christensen and Hauser, 1971a). Asa result, in the isolated intact cat colon, controlpotentials usually were propagated orally (fig 5a), butspread in either direction could occur (fig 5b). When

A

-50 _ _ J

6rOL

B Fig 2 From Christensenet al (1969). A and B:

my

o0-l--, Intracellular recordings and-f>- tension from circular

05 r muscle ofdistal colon. Note1_ that slow wave amplitude

is independent ofpresenceor absence of contractions.C: Intracellular andextracellular recordingsfrom circular muscle ofproximal colon of the cat.Extracellular recordingwith a glass pore electrode.Time constant 0 3 sec.

c

mv

0v

t0se I To.i* '_,*,lV

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Symposium on colonic function

0-3 ,uM Carbachol 1 ipM L-Hyoscyamine

0.2mvAscending r f t

0-2myvlllI:Right I ; IJ 4 4 A>Jv_<

0-2 mv

Transverse ! ,-L

Left 0 m{44

Mid 02niv1.1(1111 (hItL,hLDescending IVV''~~~ rA~4,A

Sigmoid 0 2 mv

1 minute

40

35 [co

*g30

C 20

c

cr 15

ILO

10

a5

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A

Fig 3 From Wienbeck and Christensen(1971). Simultaneous recordsfrom the sixareas of circular muscle of the cat colonin vitro as described in the text. The colonslow waves, recordedfrom glass poreelectrodes through AC amplifiers, timeconstant I sec, show at all sites the firstpositive component followed by a secondnegative component. During the controlperiod, in the record at the left, there arealmost no spikes present. After addition of0 3 ,uM carbachol to the tissue, in the middlerecord, the slow wave duration (the intervalbetween first and second slow wavecomponents) is prolonged, and numerousspikes become apparent, superimposed onslow waves. At some recording sites thefrequency ofslow waves decreases.Consecutive addition of 1 ,uM1-hyoscyamine to the tissue, in the recordat the right, shortens slow wave durationand suppresses spike activity.

Fig 4 From Christensen et al(1974). A plot of the averagefrequency ofslow waves along thecolon in vitro before and afterpartition. The vertical axis indicatesfrequency in cycles per 5 min. Thehorizontal axis shows normalizedlength of the 14 colons examined,0% at the ileocaecal junction and100% at the anal verge. The plotofaveragefrequencies beforepartition(plot B) shows a slight gradient infrequency, frequency increasing withdistance from the ileocaecal junction.The plot ofaverage frequencies afterpartition is labelled A. Brackets showI SD above and below the mean.

4

Control

0 1-10 11-20 21-30 31-40 41-50 51-60. 61-70 71-80 81-90 91-100

Percentage of total length of colon

- - a - -301

45r

E. E. Daniel

B2 m

1 mini

i,

t-_

.'t

_v!IS

-4-

:t

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*: :ok lts -- 'e -

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Fig 5 From Christensen and Hauser (1971a). A.Most common phase relationships in proximal colonof cat in vitro. Electrodes from (1) to (6) are 5 8 mmapart on exposed circular muscle. (1) is < 2 cm fromileocaecal junction. Occasional occurrence of reverse

phase relationships in a similar preparation.

proximal oscillators had phase lead, conductionvelocity was faster (3-6 versus 2-6 mm/sec) thanwhen distal oscillators had phase lead.

In situ, in the unanaesthetized cat with chronicallyimplanted bipolar electrodes (Wienbeck, 1972a), thelongitudinal electrical coupling of control potentialsseems to be tighter than in vitro, since the frequencyof oscillation of the proximal colon is higher (5-3 vs4-8 cpm), and those of the distal colon may be less(5 5 vs 5 7 cpm). These results require confirmationby comparison in simultaneous experiments.

In terms of the coupled relaxation oscillator modelof colonic activity, tight coupling is favoured by ahigh output of coupling current from the drivingoscillator, a high coupling coefficient (most of the

output of the driving oscillator reaches the input ofthe driven oscillator, owing to low resistance orimpedance between them), a small difference inintrinsic frequencies between driving and drivenoscillators, and a short refractory period in thedriven oscillator. We do not know what accountsfor the tighter coupling of colonic oscillations in thelongitudinal axis in vivo than in vitro.These results, together with the interaction of

proximal and distal oscillators, each to pull thefrequency of the other, strongly supports the exis-tence of mutual coupling of colonic slow-waveoscillators, and provide a basis for their integrativeand controlling function along the longitudinal axis.

In its transverse axis, when cat colon was cut open,laid flat, and a strip of mucosa removed (Christensenand Hauser, 1971b), coupling between oscillatorswas sufficient, in conjunction with what are probablyvery small differences in intrinsic frequency, to keepthem phase-locked 93 to 97% of the time. Noevidence of spirality of muscle was obtained. Con-duction velocity was, as expected from considerationof muscle structure and of the small differences inintrinsic frequencies, greater than in the longitudinalaxis: 7-5 to 9-6 compared with 2-3 to 2-6 mm/sec.Transverse coupling, as judged by increased conduc-tion velocities, was greater in the middle colon thanin the ascending colon (Christensen and Rasmus,1972). Tight coupling in the circular axis provides fornearly simultaneous excitation of rings of largebowel, ie, provides a basis for segmental contrac-tions.

Ionic basis of control potentialsThe conduction changes and ionic currents whichunderlie control potentials of cat colon are notknown. Early results (Wienbeck and Christensen,1971b) suggested that they depend directly orindirectly on sodium and/or calcium currents.

NERVE CONTROL SYSTEMSStudy of the actions of nerve mediators providesinsight into the potential mechanisms for neuro-genic modulation of myogenic control activity.Muscarinic cholinergic agents such as bethanechol(Wienbeck and Christensen, 1971a) which act onsmooth muscle, prolonged slow waves, and increasedthe coupling between control potentials and spikes(or response potentials-fig 3). Spikes and prolongedcontrol potentials were both associated with con-tractile responses. These responses were all blockedby atropine or hyoscine (fig 3). Similar results (slowwave duration could not be determined accurately)were obtained on intravenous infusion into intact,awake cats (Wienbeck, Christensen, and Weisbrodt,1972; Wienbeck, 1972b); there were also significant

-

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rk-0I

I

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Symposium on colonic function

decreases in frequency in vivo throughout the colon,and these were blocked by atropine.

In general, control of the rhythmic, segmentingcontractions of colon might be achieved by variationsin excitability associated with control potentialsand the coupling of increased excitability to contrac-tion by release of acetylcholine from extrinsic orintrinsic parasympathetic activity. Since controlwave and contraction frequency would be expectedto increase aborally, and since in phase-lockedregions the oral regions show phase lag, this systemshould operate to impede forward propulsion ofcolonic contents, especially in the proximal colon.

Sympathetic activity through release of norepine-phrine might have biphasic effects; in vitro, lowconcentrations of norepinephrine (01 to 10 ,uM)increased control potential duration and associatedspiking with contractions. Higher doses (3 to 100,uM) depressed spike activity (Wienbeck andChristensen, 1971a). The excitant actions were onx-adrenergic receptors. However, Hulten (1966)found that stimulation of sympathetic nerves to thecolon of anaesthetized cats caused inhibition ofcontractile activity, either spontaneous activity orthat induced by parasympathetic nerve stimulation,but not that evoked by intraarterial acetylcholine. Itis unclear whether sympathetic nerve stimulationcould ever lead to excitation of the colon in theawake animal. His results suggest sympatheticcontrol by inhibition of acetylcholine release.

PATHOPHYSIOLOGY OF DIARRHOEA ANDCONTROL POTENTIALSIn colons from cats with spontaneous diarrhoea, incolons treated in vitro with sodium ricinoleate inlow doses (> 10-7 M), in colons treated in vitro withquinine or quinidine in low concentrations, but notin colons similarly treated with sodium oleate,phase-locking ofcontrol potentials in the longitudinalaxis was diminished (Christensen, Weisbrodt, andHauser, 1972; Barker and Christensen, 1973;Christensen and Freeman, 1972). No consistentchanges in conduction velocity or frequency, or inspiking, were found. The authors termed this 'adecrease in congruence' and suggested it mightprovide an explanation for diarrhoea by interferingwith the normal frequency gradients and phaserelationships which operate to retard propulsion inthe proximal colon. The authors suggest that theunderlying mechanism might be either decreasedcoupling between oscillators, or increased frequen-cies of driven oscillators, ie, those with lowerintrinsic oscillation frequency. The latter explana-tion seems unlikely, since any decrease in thedifferences in intrinsic frequencies of oscillatorsalong the large bowel should increase phase locking.

ANOTHER ELECTRICAL CONTROL SYSTEMIn addition to slow waves (or control potentials) andspikes (or response potentials), there is anothermyogenic electrical event. In early studies (Christen-sen, Caprilli, and Lund, 1969) fast oscillatingpotentials with a frequency of 30 to 40 cycles perminute were observed; they were always associatedwith contractions (fig 6). They have not beenobserved in intracellular recordings from circularmuscle. They were at least partially independent ofcontrol potentials, since both types could occursimultaneously (see fig 5). They were usuallyslower in frequency than spikes. Fast oscillations(30 to 45 cpm) were also observed in vivo (Wienbecket al, 1972; Wienbeck, 1972a). They were oftenpreceded and followed by spikes, and sometimesspikes were superimposed on them and they, togetherwith spikes, were associated with contractions. Inthe distal colon in vivo, long spike bursts werefound, lasting up to 30 sec, not phase-locked to slowwaves, and recurring at 0-7 to 1-5 cpm. Recently, itwas observed (Christensen et al, 1974) that in vitrothese spike bursts migrate (70% aborally) and thattheir electrical signal in the proximal colon is thefast oscillating potential. They were longer in dura-tion in the distal colon. All migrating spike burstswere abolished by transection of the intestine.

It was suggested (Christensen et al, 1974; Wien-beck, 1972a) that the migrating spike burst issimilar to the 'interdigestive migrating spike complex'of the dog and cat small intestine (Szurszewski, 1969;Weisbrodt and Christensen, 1972), and perhapsbetter called 'activity front' since they are notsuppressed by feeding in all species (Grivel andRuckebusch, 1972). This has recently been con-firmed (Wienbeck and Janssen, 1974); spike burstsmigrating into the cat colon in vivo from the ileuminduce oscillatory potentials in the colon. Spikebursts and/or oscillations usually do not migratefrom colon to ileum, but do migrate orad into thecaecum. Such spike bursts are induced within 20minutes by feeding or gastrin, followed by local non-migrating spiking. This may provide a basis for thecontrol of motility called the 'gastro-ileal' and'gastro-colic' reflexes.

Migrating spike bursts can start within the colon,usually in the mid- or proximal colon, and mostoften move aborally3. They could provide a basis forthe control of 'peristaltic' or mass movements, butthe propagation velocity seems slow for mass

9Recordings with microelectrodes in the distal rabbit colon (Gillespie,1968) or with glass suction electrodes from the serosal surface ofmouselarge intestine (Wood, 1974) showed slow waves, usually with phase-locked spikes; sometimes there were in the mouse intestine rapidoscillations usually obliterating slow waves but associated with spikes.Thus the components of the cat electrogram may occur in otherspecies.

303

E. E. Daniel

Qmv __

05r

1or 10sec

0'-05r

0v.......r .

Fig 6 From Christensen et al (1969). Relationship between slow waves, the oscillationphenomenon, and contractions. All three panels represent different segments ofa recordfroma strip ofproximal colon. Time scale at top shows seconds. Upper channel is the recordfromone glass-pore electrode; lower channel records tension of the strip. In A and B, slow wavesaccompany rhythmic contractions of varying magnitude. In C, a prolonged powerful toniccontraction accompanies oscillations in electrical record which do not prevent occurrence ofnewslow waves.

movements, and mass movements are usuallyassociated (in man, at least) with relaxation ratherthan with contraction of most of the colon.

Human Colon

MYOGENIC CONTROL SYSTEMAt present, we are uncertain about the nature andorigins of the human colonic electromyogram. Somerecordings in the literature cannot be interpretedbecause essential information about recordingparameters (such as the time constant in RC coupledtracings) were not stated.Most records in vivo have been obtained from the

more readily accessible distal large bowel, ie, therectum or descending colon. They have usually beenobtained with monopolar or bipolar suction-typeelectrodes on the mucosal surface. The intent ofsuch recordings is to force ring electrodes tightagainst the mucosa, or to push fine needle electrodesthrough the mucosa and into the circular muscle,and maintain this as a stable contact. Success insuch intentions has not been ascertained, ie, it isnot clear whether variable contact and shortcircuiting occur. Also, real differences in electricalactivity may occur between regions of fixed segmen-tal contraction and other regions.

Several observations have been made consistently:1 The slow waves are not recorded continuously,but appear and disappear (Wankling, Brown,Collins, and Duthie, 1968; Kerremans, 1968, 1969;Couturier, Roze, Couturier-Turpin, and Debray,1969; Ustach, Tobon, Hambrecht, Bass, andSchuster, 1970; Taylor, Smallwood, and Duthie,1974), and when present they appear to wax andwane (fig 7). In the distal colon, slow waves werepresent 5-5 to 21 % of the time (Couturier et al,1969; Taylor et al, 1974); in the rectum they werepresent 72 to 92% of the time (Kerremans, 1968,1969; Ustach et al, 1970; Taylor et al, 1974). In avery recent study two slow wave frequencies were dis-tinguished: one was 3 to 4 cpm; the other (recordedmore frequently) was 6 to 9 cpm; and the frequencyshowed a tendency to increase with increasing dis-tance from the anus. The percentage of time in whichthe flow waves could be recorded was 70% at 5 cmfrom the anus, decreasing to less than 20% at 30cm above the anus (Taylor et al, 1974).

2 In the rectum (Taylor et al, 1974) and distalcolon (Couturier et al, 1969; Kerremans, 1968, 1969)slow waves and spikes are recorded by some investi-gators. In the distal colon (Couturier et al, 1969)slow waves and spikes corresponded in frequency(10/min); spikes occurred at any phase of the low

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Fig 7 From Couturier et al (1969). Recording from a unipolar suction typeelectrode (reference electrode on upper thigh) in a normal human colon. Channels2 and 3 from the same electrode: 2 with a bandpass from 0-2 to 100 cps at 3 dB;3 with a band pass from S to 100 cps. Channel I shows intraluminal pressure(1 mB = 0'750 nun Hg). In places a clear synchronization ofspike bursts (inchannel 3) and slow waves (in channel 2) was observed. However, spike burstswere not usually synchronous with pressure increases.

wave, but in the figures shown (eg, fig 7) were mostoften at the positive phase of the slow wave (Coutu-rier et al, 1969). In the rectum, the slow waves andspike bursts often corresponded in frequency (2A4 to5'2 cpm), and though spikes usually occurred in thepositive phase of the slow wave, they could occur atany phase (Kerremans, 1968, 1969).

3 In a study of the 'rectal canal' (Wankling et al,1968), slow waves with a frequency of 14-6 to 16A4cpm were obtained without spikes being recorded.These values were close to those reported (17-5 and18-9 cpm) in another study from the internal analsphincter (Kerremans, 1968, 1969); and the descrip-tion in this paper suggests that in fact both studieswere from the internal anal sphincter. If so, bothagreed about the absence of any recordable spikes inthis region associated with contraction. Both alsoagree that there are ultraslow variations in electricalpotentials in the internal sphincter; one group founda frequency of 2 7 to 3 2 cpm (Kerremans, 1968,1969); the other found a frequency of 1 2 to 1 6cpm, and sometimes found them to be associatedwith contraction (Wankling et al, 1969). The formergroup (Kerremans, 1969) also found ultraslow wavesof similar frequency in the rectum, and postulatedthat they were propagated into the internal sphincter.A third group (Ustach et al, 1970) has also recordedfrom the internal sphincter and reported a frequencyof about 17 cpm in normal patients (lower frequen-cies were found in patients with functional andneurological disorders). This group, too, failed torecord any spike activity, even during contraction;

and, like one of the others (Kerremans, 1968, 1969),found that slow waves disappeared during relaxa-tion of the sphincter evoked by rectal distension.From these data it is premature to conclude that

the slow waves are, indeed, absent a large part of thetime. They may be lost because of asynchrony(absence of phase locking) in the regions from whichrecordings were made, and because of technicaldifficulties in recording with constant contact andwith adequate sensitivity from the mucosal surfacein vivo. The higher frequency of occurrence of slowwaves in the distal colon and rectum may be relatedto the fusion in that region of taenia to form a regularand continuous longitudinal muscle.

It is also premature to conclude that the slowwaves are also control potentials in the sense alreadyfound for stomach, small intestine, and cat colon.The relationships between slow waves and spikes,and between spikes or slow waves and contraction,remain to be established. Possibly slow waves of thehuman colon, like those of the guinea pig smallintestine (Bolton, 1971), are induced by acetyl-choline release.To ascertain the nature and control functions of

electrical activity of the muscle layers of the humancolon, in-vitro studies with and without mucosa, withintra- and extracellular electrode recordings, areneeded. Such studies present formidable difficulties,eg, obtaining normal tissues, keeping them in goodphysiological condition despite their thickness andthe need for dissection, etc. None of these difficultiesis insurmountable. Data (mentioned above) from

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306 E. E. Daniel

in-vivo studies are subject to difficulties in inter-pretation which will be overcome only by carefulstudies in vitro.The nature of neuronal and hormonal controls as

they may interact with the myogenic control systemin the human colon is also unknown. However, itseems clear that the conceptual and experimentaltools for analysis of the myogenic, neuronal, andhormonal control of human colonic motility are athand, waiting for use. Within the next five years anadequate description of these could be available.Such a description of normal control would help inthe understanding of disordered control in disease.References

Barker, D., Jr., and Christensen, J. (1973). Some effects of quinidineand quinine on the electromyogram of the colon. Gastro-enterology, 65, 773-777.

Belisle, S., and Gagnon, D. J. (1971). Stimulating action of catechol-amines on isolated preparations of the rat colon and humanand rabbit taeniae coli. Brit. J. Pharmacol., 41, 361-366.

Bennett, A., and Whitney, B. (1966). A pharmacological study of themotility of the human gastrointestinal tract. Gut, 7, 307-316.

Bolton, T. B. (1971). On the nature of the oscillations of the membranepotential (slow waves) produced by acetylcholine or carbacholin intestinal smooth muscle. J. Physiol. (Lond.), 216, 403-418.

Bucknell, A., and Whitney, B. (1964). A preliminary investigation ofthe pharmacology of the human isolated taenia coli prepara-tion. Brit. J. Pharmacol., 23, 164-175.

Burnstock, G. (1972). Purinergic nerves. Pharmac. Rev., 24, 509-581.Christensen, J., Anuras, S., and Hauser, R. L. (1974). Migrating spike

bursts and electrical slow waves in the cat colon: effect ofsectioning. Gastroenterology, 66, 240-247.

Christensen, J., Caprilli, R., and Lund, G. F. (1969). Electrical slowwaves in circular muscle of cat colon. Amer. J. Physiol., 217,771-776.

Christensen, J., and Freeman, B. W. (1972). Circular muscle electro-myogram in the cat colon: local effect of sodium ricinoleate.Gastroenterology, 63, 1011-1015.

Christensen, J., and Hauser, R. L. (1971a). Longitudinal axial couplingof slow waves in proximal cat colon. Amer. J. Physiol., 221,246-250.

Christensen, J., and Hauser, R. L. (1971b). Circumferential couplingofelectric slow waves in circular muscle of cat colon. Amer. J.Physiol., 221, 1033-1037.

Christensen, J., and Rasmus, S. C. (1972). Colon slow waves: size ofoscillators and rates of spread. Amer. J. Physiol., 223, 1330-1333.

Christensen, J., Weisbrodt, N. W., and Hauser, R. L. (1972). Electricalslow wave of the proximal colon of the cat in diarrhea.Gastroenterology, 62, 1167-1173.

Couturier, D., Roz6, C., Couturier-Turpin, M. H., and Debray, C.(1969). Electromyography of the colon in situ: an experimentalstudy in man and in the rabbit. Gastroenterology, 56, 317-322.

Daniel, E. E. (1973). A conceptual analysis of the pharmacology ofgastrointestinal motility. In International Encyclopedia ofPharmacology and Therapeutics, Sect. 39a, Motility and Secretionedited by Pamela Holton. Vol. 2, pp. 457-545. PergamonPress, Oxford.

Elsen, J., and Arey, L. B. (1966). On spirality in the intestinal wall.Amer. J. Anat., 118, 11-20.

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