Thallium, Effects on Mitochondria

Cross-References

▶ Potassium in Biological Systems

▶Metals and the Periodic Table

▶Thallium, Distribution in Animals

▶Thallium, Effects on Mitochondria

References

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Thallium, Effects on Mitochondria

Sergey M. Korotkov

Sechenov Institute of Evolutionary Physiology

and Biochemistry, The Russian Academy of Sciences,

St. Petersburg, Russia

Synonyms

Thallium: Thallium(I), Tl(I), Tl+; Effects: Biological

action, Influence; Mitochondria: Intracellular organ-

elles, Organoids

Definitions

Thallium: Thallium is a metal with atomic number of

81 and two oxidation states of +1 and +3. Thallium

belongs to the group of trace elements and is used in

the electronics industry, in the pharmaceutical industry

(with care), and in glass manufacturing. Thallium is

highly toxic and was used in rat poisons and

insecticides.

Mitochondria: Mitochondria are two-membrane

granular or prolate organelles of 0.5 mm size which

are located between the cytoplasm and nuclear mem-

branes of the majority eukaryotic cells of both auto-

troph (photosynthesizing plants) and heterotroph

(mushrooms and animal) organisms. The basic function

of mitochondria is oxidation of organic compounds

following use of energy, released at their disintegration,

in creation of both the proton gradient and electrochem-

ical potential on the inner mitochondrial membrane for

the purpose of ATP synthesis which occurs by the

mitochondrial H(+)-ATP-synthase.

Thallium, Effects on Mitochondria 2193 T

T

Additional Definitions

Mitochondrial swelling: Mitochondrial swelling was

evaluated as a decrease in A540 at 20�C using a SF-46

spectrophotometer (LOMO, St. Petersburg, Russia).

Mitochondrial respiration: Mitochondrial respira-

tion (oxygen consumption rate) was measured polaro-

graphically by using LP-7 (Czechoslovakia) in a 1.5-ml

closed thermostatic chamber with magnetic stirring

at 26�C.Respiratory states: Respiratory states have been

defined by Chance and Williams (1956) according to

a protocol for oxygraphic experiments with isolated

mitochondria. State 3 is defined as the state after addi-

tion of ADP and state 4 as one after phosphorylation of

all ADP to ATP.

Mitochondrial membrane potential: Mitochondrial

membrane potential (DCmito) was evaluated as an

intensity of safranin fluorescence (arbitrary units) in

the mitochondrial suspension with magnetic stirring at

20�C using a Shimadzu RF-1501 spectrophoto-

fluorimeter (Shimadzu, Germany) at 485/590 nmwave-

length (excitation/emission).

Effects of Thallium on Cells and LivingOrganisms

Thallium is a highly toxic metal which belongs to

a group of trace elements. Human toxicity was found

in use of Tl compounds as a human depilatory (thal-

lium acetate), a component in manufacturing of optical

glasses (thallium oxide), a homicidal agent, and

a rodenticide (thallium sulfate) to kill rats, mice, and

other animals. After penetrating into an organism, Tl

damages cardiovascular, central nervous, and renal

systems as well as the gastrointestinal system and

skin, and it results in hair loss (Goel and Aggarwal

2007 and references herein). It has been shown that the

essence of the harmful effects of Tl+ on living organ-

isms lies in its ability both to easily penetrate the inner

mitochondrial membrane (Saris et al. 1981; Korotkov

et al. 2008 and #3 ref. herein) and to substitute K+ in

K+-dependent enzymes and biochemical processes

(Douglas et al. 1990). These effects of Tl+ resulted in

both the proximity of crystal-chemical radii of K+ and

Tl+, and easy thallium polarizability that allows Tl+

to form manifold chemical bonds with reactive groups

of molecules which constitute living organisms.

Experiments with rats, exposed to chronic thallium

intoxication in vivo, showed that Tl+ stimulated mas-

sive mitochondrial swelling which was followed by

disruption of mitochondrial and other intracellular

membranes of kidney, liver, brain, and other organs

(Korotkov et al. 2008, refs. of #9 and #10 herein). Tl+

has triggered apoptosis in Jurkat and PC12 cells

(Bragadin et al. 2003; Hanzel and Verstraeten 2009).

It was postulated earlier that Tl+ can stimulate release

of Ca2+ from intracellular compartments (Korotkov

et al. 2008, #9 ref. herein). Increase of cytoplasmic

concentration of Ca2+, Na+, or Pi and decrease of one

of K+ were both found in experiments with isolated rat

hepatocytes in medium containing TlCl. Interaction of

Tl+ with SH groups of mitochondrial and cellular

membranes, glutathione depletion, and the increased

production of reactive oxygen species can be among

other reasons of the thallium toxicity (Zierold 2000;

Korotkov et al. 2008, #9 ref. herein; Hanzel and

Verstraeten 2009). It was quite recently shown that

Tl+ could injure isolated rat hepatocytes that resulted

in hepatocyte proteolysis, in glutathione depletion, in

decline of the inner mitochondrial membrane potential

(DCmito), in ROS formation, and in lipid peroxidation

(Pourahmad et al. 2010).

Influence of Tl+ on Isolated Mitochondria

The study of swelling of isolated mitochondria in

nitrate media showed that the inner mitochondrial

membrane (IMM) is poorly penetrated by univalent

cations such as H+, K+, and Na+. However, visible

swelling of the mitochondria in TlNO3 medium

(Fig. 1) exposed substantial permeability of the mem-

brane to Tl+ (Saris et al. 1981; Korotkov et al. 2008).

Subsequent energization of the mitochondria stimu-

lated their massive contraction which occurred by

means of a Tl+/H+ exchange mechanism (Saris et al.

1981; Korotkov et al. 2008). Nonenergized mitochon-

dria in Tl acetate medium showed massive swelling

that was realized by means of Tl+/H+ exchange (Saris

et al. 1981; Korotkov et al. 2007). Further energization

of the mitochondria stimulated additional swelling due

to an electrophoretic uniport of Tl+ into the matrix

(Saris et al. 1981; Korotkov et al. 2007; Korotkov

et al. 2008, #3 ref. herein). The participation of the

mitochondrial KATP-dependent channel in the electro-

phoretic uniport of Tl+ in the matrix was demonstrated

T 2194 Thallium, Effects on Mitochondria

in both swelling and fluorescent experiments

(Wojtovich et al. 2010 and #45 ref. herein). Tl+

resulted in both the increase of state 4 respiration of

rat liver mitochondria (Fig. 2), and potent futile

cycling of Tl+ via the IMM (Bragadin et al. 2003;

Korotkov et al. 2007; Korotkov et al. 2008 and #3

ref. herein). Nonactin, a cyclic ionophore, and inor-

ganic phosphate (Saris et al. 1981; Korotkov et al.

2007; Korotkov et al. 2008 and #12 ref. herein) have

both facilitated transport of Tl+ into mitochondria and

increased both state 4 and swelling of mitochondria

(Figs. 1 and 2). With lower affinity to molecular

SH groups, Tl+ unlike bivalent heavy metals (Cd2+,

Zn2+, Hg2+, Cu2+, and Pb2+) has not inhibited state 3

or 2,4-dinitrophenol (DNP)-stimulated respiration

in medium containing TlNO3 or Tl acetate (Figs. 1

and 2) owing to the lack of inhibition of mitochondrial

respiratory enzymes by thallium (Korotkov et al. 2007;

Korotkov et al. 2008 and refs. of #3 and #10 herein;

Korotkov 2009).

Tl+ Increases the Permeability of the InnerMitochondrial Membrane to UnivalentCations (H+, K+, Na+, and Li+)

It was quite recently shown in experiments using

media containing nitrate salts of univalent cations

and TlNO3 (Korotkov 2009; Korotkov and Saris

2011) that Tl+ similar to the bivalent heavy metals

increased the permeability of the inner membrane of

rat liver mitochondria to univalent cations (H+, K+,

Na+, and Li+). The Tl+-induced increase of the perme-

ability (for more details, see Korotkov 2009 and

RLMRLM

RLM

RLM

SuccSucc

Succ Succ

25 25

50

50

75

75

0.052 min

0.05

2 min

ΔA540

ΔA540 ΔA540

ΔA540

50

75

75

0.1 0.1

3 min 3 min

0, 5, 1015

51015025

50

25

Pia b

c d

Thallium, Effects on Mitochondria, Fig. 1 Effects of Tl+ on

swelling of rat liver mitochondria in a 160 mOsm nitrate

medium. Mitochondria (1.5 mg protein/ml) were added to the

medium containing 5–75 mM TlNO3, as well as 5 mM Tris-NO3

(pH 7.3), 1 mM Tris-PO4 (b), 10�8 M nonactin (d), 4 mMrotenone, and 3 mg/ml of oligomycin. To obtain 160 mOsm,

sucrose is added to the medium. Additions of mitochondria

(RLM) and 5 mM succinate (Succ) are shown by arrows. Typ-ical traces for three different mitochondrial preparations are

presented. Concentrations of TlNO3 (mM) are shown on the

right of the traces (This material is reproduced with the courte-

ous permission of John Wiley & Sons, Inc. See Korotkov et al.

2008 and #6 ref. herein)


T

a b

c d

e f

125

100

75

50

25

00

0

0 25 50 75

0 0

50

100

150

200

250

300

350

0

50

100

150

200

250

50

100

150

200

10 20 30

TI-acetate (mM)

ng a

tom

O/m

in /m

g of

pro

tein

ng a

tom

O/m

in /m

g of

pro

tein

ng O

/min

/mg

of p

rote

in

0

50

100

150

200

250

ng a

tom

O/m

in/m

g of

pro

tein

40 50 0 10 20 30

TI-acetate (mM)

40 50

0 10 20 30

TI-acetate (mM)

40 50

25 50

St 4 St 4 + DNP

St 4 + DNP

St 3

St 4

St 4 1

2

3

St 4 + DNP

St 3

2

2

2

2

1

1

1

1

2

1

TINO3 (mM)

TINO3 (mM)

ngat

om O

/min

/mg

of p

rote

in

150

200

250

300

100

50

0

ngat

om O

/min

/mg

of p

rote

in

75 100 125 0 25 50

TINO3 (mM)

75 100 125


oxygen consumption rates (ng atom O min/mg of protein) of rat

liver mitochondria in a 290 mOsm medium. Mitochondria

(1.5 mg protein/ml) were suspended in the medium containing

5 mM Tris-NO3 (pH 7.3) and 0–125 mM TlNO3 (a, b, e) or5 mM Tris acetate (pH 7.3) and 0–50 mM Tl acetate (c, d, f) aswell as 3 mM Mg(NO3)2 (c–f), 5 mM succinate, and 4 mMrotenone. Additionally the medium was supplemented with

3 mM Tris-PO4 (a–b [trace 2], and e–f) and 10�8 M nonactin

(c–d, f [trace 2]). To obtain 290 mOsm, sucrose was added to the

medium; 130 mM ADP or 30 mM DNP was added to the media

after 2 min recording of state 4 to induce state 3 or DNP-

stimulated respiration. Error bars were calculated by the Muller

formula from rates found for three different mitochondrial prep-

arations (see Korotkov 2009) (This material is reproduced with

the courteous permission of both John Wiley & Sons, Inc. (a–d,f) and Springer (e). See Korotkov et al. 2008 and #6 ref. herein;

Korotkov 2009)


Korotkov and Saris 2011) was showed by the risen

swelling of both non-energized (Fig. 3) and energized

mitochondria, and by the accelerated dissipation of

DCmito (Fig. 4). Contraction of succinate-energized

mitochondria, swollen in the nitrate medium (Fig. 3d)

but not sucrose one (Fig. 3c), was inhibited by quinine,

which blocks mitochondrial K+/H+ exchange

(Korotkov 2009). The participation of the exchanger

in extruding the Tl+-induced excess concentration of

the univalent cations from the matrix was early

hypothesized (Saris et al. 1981; Korotkov et al.

2008). The Tl+-induced swelling of succinate-

energized mitochondria resulted in the decrease of

state 3 and 2,4-dinitrophenol (DNP)-stimulated respi-

ration (Fig. 4b) (more detail see Korotkov 2009).

Thallium Induces the PermeabilityTransition in the Inner Membrane ofCa2+-Loaded Rat Liver Mitochondria

It is known that binding of Ca2+ with matrix calcium-

specific trigger sites, located near the adenine

nucleotide translocase (ANT), with following fall of

DCmito triggers opening of the mitochondrial perme-

ability transition pore (MPTP) in the inner membrane

which becomes permeable to molecules up to

1,500 kDa. The pore opening results in massive

mitochondrial swelling, lowering of the matrix con-

centration of Ca2+ and ATP, and dissipation of the

DCmito. If the Ca2+ sites are insufficiently saturated,

MPTPs are opened in the low conductance state

and small molecules up to 300 kDa or ions

(H+, K+, and Ca2+) may penetrate easily the IMM.

In the earlier times, it was believed that the MPTP

is formed by ANT, cyclophilin D (CyP-D),

and the voltage-dependent anion channel (VDAC).

In modern times, many researchers consider the

mitochondrial phosphate carrier and CyP-D to be

primary components of the MPTP, whereas ANT is

viewed as a regulatory part of the MPTP.

It was recently showed that Tl+ has induced opening

of the MPTP in Ca2+-loaded rat liver mitochondria

(CaRLM) energized by glutamate plus malate or suc-

cinate which are substrates of I and II respiratory

complexes, respectively (Figs. 5–7) (for more details,

RLM Succ

RLMSucc

RLM

Succ

0255075

0.03

0.1

2 min

2 min

ΔA540

ΔA5400.1

2 min

ΔA540

RLM Succ

0

25

50

750.03

2 min

ΔA540

0500

0150

5001000

a b

c d


swelling of rat liver mitochondria in a 400 mOsm medium.

Mitochondria (1.5 mg protein/ml) were added to the medium

containing 0–75 mM TlNO3 (a–b) or 75 mM TlNO3 and

50–1,000 mM quinine (c–d) as well as 5 mM Tris-NO3 (pH

7.3), 250 mM sucrose (a, c), 125 mM of KNO3 (b, d), 4 mMrotenone, and 3 mg/ml of oligomycin. To obtain 400 mOsm,

sucrose was added additionally to the medium. Numbers near

the traces show concentrations of TlNO3 (mM) or quinine (mM)

on panels A and B or C and D, correspondingly. Additions of

mitochondria (RLM) and 5 mM succinate (Succ) are shown by

arrows. Typical traces for three different mitochondrial prepa-

rations are presented (This material is reproduced with the cour-

teous permission of Springer. Korotkov 2009)


T

see Korotkov and Saris 2011). This effect of Tl+ in the

nitrate media resulted in both the increased swelling

(Figs. 5 and 6), as well as the accelerated dissipation of

DCmito and the decreased state 4, or state 3, or DNP-

stimulated respiration (Fig. 7). It should be stressed

that the swelling of nonenergized mitochondria was

stimulated by both Tl+ and Ca2+ in the media free of

rotenone (Fig. 5). However, the swelling was increased

by Tl+ but not Ca2+ in the presence of rotenone (Fig. 6).

It is possible that these differences may be due to the

induction of energy-dependent uptake of Ca2+ together

with the participation of mitochondrial endogenous

substrates under conditions in which pyridine nucleo-

tides are in a more oxidized state. One can see on

Figs. 5 and 6 that Tl+ distinct from the bivalent heavy

metals can stimulate opening of the MPTP only in the

presence of Ca2+. The most probable reason is: Tl+

reacts poorly with the Ca2+-binding sites as it has

60

40

200 25 50 75

TINO3(mM) TINO3(mM)0 25 50 75

121086420200

300

400

500

600

700

800

900

1000

Time (min) Time (min)

6

4 43

3

1 1

2 25

5

121086420

400

500

600

700

800

900

1000 Succ

FccpQui

Fccp

Succ

Qui

Saf

rani

n flu

ores

cenc

e (a

rbitr

ary

unite

s)

Saf

rani

n flu

ores

cenc

e (a

rbitr

ary

unite

s)

100

150

200

250

ng O

/min

/mg

of p

rote

in

ng O

/min

/mg

of p

rote

in

St 4St 4 + DNPa

2

2

1

1

b

c

Sucrose

d

Thallium, Effects on Mitochondria, Fig. 4 Effects of TlNO3

on oxygen consumption rates (ng atomOmin/mg of protein) and

the inner membrane potential (DCmito) of rat liver mitochondria

in a 400 mOsm medium. Mitochondria (0.5 (c–d) or 1.5 (a–b)mg protein/ml) were suspended in the medium containing:

0–75 mM (a–b) or 30 mM (c–d) of TlNO3, 5 mM Tris-NO3

(pH 7.3), 250 mM sucrose (a–b [trace 1], and c), 125 mMKNO3

(a–b [trace 2], and d), 5 mM succinate (a–b), 4 mM rotenone, and

3 mg/ml of oligomycin, as well as 1mMTris-PO4 (c–d) and 3 mMsafranin (c–d). To obtain 400 mOsm, sucrose was added addi-

tionally to the medium (Figs. 4–7). DNP of 30 mM (b) was added

to the medium to trigger DNP-stimulated respiration after 2 min

recording of state 4 (a). Error bars (a–b) were calculated by the

Muller’s formula from rates found for three different mitochon-

drial preparations. Additions before mitochondria (c–d) were asfollows: 1, none (free of TlNO3); 2, none (marked in bold); 3,5 mMMg(NO3)2; 4, 2 mM ADP; 5, 500 mM (d) or 1,000 mM (c)quinine [traces 1 and 5]; 6, 0.5 mM ADP, 1 mMMg(NO3)2, and

1 mM CsA. Typical traces for three different mitochondrial

preparations are presented (This material is reproduced with

the courteous permission of Springer. Korotkov 2009)


a single charge and shows comparatively low affinity

to molecular SH groups. The phenomenon of the sub-

strate specificity manifested in the fact that the total

concentrations of Ca2+ stimulated the maximum swell-

ing of mitochondria energized by glutamate plus

malate (Fig. 5), but not by succinate plus rotenone

(Fig. 6). The possible roles of Ca2+-binding sites,

located near the respiratory complex I, and the ANT

in inducing opening of the MPTP are discussed

(Korotkov and Saris 2011).

It was discovered that the Tl+-induced MPTP in

CaRLM was potentiated by inorganic phosphate and

diminished by the MPTP inhibitors (ADP, CsA, Mg2+,

Li+, rotenone, EGTA, and ruthenium red) (Korotkov

et al. 2008; Korotkov 2009; Korotkov and Saris 2011).

The Tl+-induced swelling of CaRLM, energized by

glutamate plus malate (Fig. 5) or succinate in the

presence of rotenone (Fig. 6), was reduced by ADP,

CsA, Mg2+, or ruthenium red, an inhibitor of the mito-

chondrial Ca2+ uniporter. The MPTP inhibitors

prevented both the decreased DNP-stimulated respira-

tion and the fall of DCmito in succinate-energized

CaRLM (Fig. 7). Maximal effect was found in the

simultaneous presence of ADP and CsA in the

RLM

RLMRLM

Mg+ADP+CsAADP+CsAMg+CsA

Mg+ADPADP

control

Mg+CsA Mg+ADP+CsA

ADP+CsACsA RR

control

MgADP

Mg+ADP

Mg

RR

CsA

2 min

0.1Δ A540

G + M RLM G + M

G + M

KNO3

KNO3

G + M

0 +100 0 +100

25 +100

75 + 0

50 + 50

50 + 100

75 + 25

75 + 5075 + 7575 + 100

25 +10075 + 0

75 + 25

50 + 50

75 + 5075 + 7575 +100

Sucrose

a b

dc

Sucrose

50 + 100

Thallium, Effects onMitochondria, Fig. 5 Effects of Tl+ and

Ca2+ on swelling of rat liver mitochondria in the presence of

glutamate and malate. Mitochondria (1.5 mg protein/ml) were

added to the 400 mOsm medium containing 0–75 mM (a–b) or50 mM (c–d) of TlNO3, 5 mM Tris-NO3 (pH 7.3), 0–100 mM(a–b) or 100 mM (c–d) of Ca2+, and 1 mg/ml of oligomycin, as

well as 250 mM sucrose (a) or 125 mM KNO3 (b). The numbers

on the right of the traces (a–b) show concentrations of TlNO3,

(mM) [in bold] or CaCl2 (mM) [in italics] in this medium.

Additions before mitochondria are indicated on the right of the

traces (c–d): none (control); 1 mM CsA (CsA); 0.5 mM ADP

(ADP); 3 mM Mg2+ (Mg); 7 mM RR (RR). Injections of mito-

chondria (RLM) and 5 mM of glutamate and malate (G + M) are

shown by arrows. Typical traces for three different mitochon-

drial preparations are presented (This material is reproduced

with the courteous permission of Springer. Korotkov and

Saris 2011)


T

media (Figs. 5–7). It was suggested that swelling of

energized mitochondria in the nitrate media containing

Ca2+ and Tl+ may be caused by opening of CsA-

inhibited and ADP-dependent pores in the IMM (for

more details, see Korotkov and Saris 2011). The Tl+-

induced swelling was inhibited by both Li+ (Korotkov

and Saris 2011) and Mg2+ (Figs. 5–7) that is possibly

related to the involvement of Ca2+ sites on the outer

surface of the IMM in opening the MPTP. The

decrease of state 4 and DNP-stimulated respiration of

CaRLM (Fig. 7) is related to the increased swelling of

the mitochondria (Fig. 6) that may be associated with

the reduced activity of the respiratory enzymes

because the mitochondrial structure can be disturbed

by the more massive swelling of CaRLM (Korotkov

and Saris 2011). Comparing experiments with the

sucrose and KNO3 media (Figs. 5 and 6), one can

conclude that Tl+, similar to Cd2+ and Ca2+, induces

opening of theMPTP less actively in the high conduction

states and furthermore, that this effect of Tl+ occurs in the

presence of the substrates of respiratory complex

I (glutamate plus malate) and II (succinate). Thus, it

RLM RLMSucca b

c dRLM

Succ

ADP(2) ADP+CsAMg+CsA

CsA

Mgcontrol

MgCsA

Mg+CsA

Mg+ADP+CsAADP+CsAADP(2)Mg+ADPnone CaADP

control

0.1

2 min

Δ A540

ADPnone Ca

Succ

RLMSucc

0 +10025 +100 50 +10050 + 50

75 + 25

75 + 0

75 + 50

75 + 7575 + 100

0 +10025 +10050 + 50

75 + 25

75 + 50

75 + 75

50 + 100

75 + 100

75 + 075 + 0

Sucrose

Sucrose

KNO3

KNO3

Thallium, Effects onMitochondria, Fig. 6 Effects of Tl+ and

Ca2+ on swelling of rat liver mitochondria in the presence of

succinate. The medium, additions, and designations are as

shown in the Fig. 5. Exceptions from Fig. 5 are that 5 mM

succinate and 2 mM rotenone were used there instead of 5 mM

of glutamate plus malate; 75 mM TlNO3 was used in experi-

ments with the MPTP inhibitors (c–d). Typical traces for threedifferent mitochondrial preparations are presented (This mate-

rial is reproduced with the courteous permission of Springer.

Korotkov and Saris 2011)


57

5776

53

RLMa

c d

bRLM

DNP

KNO3

KNO3

Sucrose

Sucrose

SuccSucc

DNP

Mg+ADP+Cs

Mg+ADP+Cs

Mg+ADP

Mg+ADP

Mg

MgADP

ADP

400 ngatom O

2 min

0 2 4 6 8 10 12

Saf

rani

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e (a

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400

600

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531

2

4FCCP

FCCP

Time (min)

200

400

600

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1000

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4

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3 5

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Time (min)

control

control

CsA

CsA

Pi

Pi

Ca2+

Ca2+

Ca2+

Ca2+

53

10994

139

5254

54

138

175

211

177

223

67

113 (190)

(208)

(211)

(181)

152(162)

(138)

64

(169)

(76)71

71

65

60

49

(49)

(49)

47

{21}

{145}

4877

80

9055

45

62

62(63)

(75)

97

17

3877

4472

{28}

{190}

64

59

8361

61

5399

5185

65

53

45

79

54

113

105

4373

5757

56

79

58

124

56(60)

(122)

(122)

(124)

(110)(121)

(94)

(83)

(133)

(51)(54)

(55)

(59)

(63)

(66)

(54)(41)

59

(57)

(57)

65(66)

(57)

(57)

(60)

(59)

(55)

57(52)

Thallium, Effects on Mitochondria, Fig. 7 Effects of TlNO3

and Ca2+ on oxygen consumption rates (ng atom O min/mg of

protein) and the inner membrane potential (DCmito) of rat liver

mitochondria in a 400 mOsm medium. The medium, additions,

and designations are as in the Fig. 4. Exception from Fig. 4 is

that additions of trace 5 on Fig. 7 are the same ones of trace 6 on

Fig. 4. The rates are presented as numbers placed above exper-

imental traces. Numbers in parentheses were obtained from

experiments with Ca2+-free media. The numbers in braces

were calculated from experiments with the Ca2+-free media,

where 75 mM TlNO3 was substituted by 150 mM sucrose

(Korotkov 2009). Accessorial additions of 30 mM (d) and

50 mM (c), or 100 mM (a–b) [traces 2–5] of Ca2+ (Ca2+) are

correspondingly shown by short (c–d) or long bold (a–b)arrows. Typical traces for three different mitochondrial prepa-

rations are presented (This material is reproduced with the cour-

teous permission of Springer. Korotkov and Saris 2011)


T

can be postulated that opening of the MPTP can play an

important role in the development of toxic processes

during thallium intoxication in living organisms

(Bragadin et al. 2003; Korotkov et al. 2008; Korotkov

2009; Pourahmad et al. 2010; Korotkov and Saris 2011).

Cross-References

▶Ca2+

▶ Sodium-Hydrogen Exchangers, Structure and

Function in Human Health and Disease

▶Tobacco

References

Bragadin M, Toninello A, Bindoli A et al (2003) Thallium

induces apoptosis in Jurkat cells. Ann N Y Acad Sci

1010:283–291

Chance B, Williams GR (1956) The respiratory chain and

oxidative phosphorylation. Adv Enzymol 17:65–134

Douglas KT, Bunni MA, Baindur SR (1990) Thallium in bio-

chemistry. Int J Biochem 22:429–438

Goel A, Aggarwal P (2007) Pesticide poisoning. Natl Med

J India 20:182–191

Hanzel CE, Verstraeten SV (2009) Tl(I) and Tl(III) activate both

mitochondrial and extrinsic pathways of apoptosis in rat

pheochromocytoma (PC12) cells. Toxicol Appl Pharmacol

236:59–70

Korotkov SM, Glazunov VV, Yagodina OV (2007) Increase

in toxic effects of Tl+ on isolated rat liver mitochondria

in the presence of nonactin. J Biochem Mol Toxicol

21:81–91

Korotkov SM (2009) Effects of Tl+ on ion permeability,

membrane potential and respiration of isolated rat liver

mitochondria. J Bioenerg Biomembr 41:277–287

Korotkov SM, Saris NE (2011) Influence of Tl+ on

mitochondrial permeability transition pore in Ca2+-

loaded Rat liver mitochondria. J Bioenerg Biomembr

43:149–162

Korotkov SM, Emel’yanova LV, Yagodina OV (2008)

Inorganic phosphate stimulates the toxic effects of Tl+

in rat liver mitochondria. J Biochem Mol Toxicol

22:148–157

Pourahmad J, Eskandari MR, Daraei B (2010) A comparison of

hepatocyte cytotoxic mechanisms for thallium (I) and thal-

lium (III). Environ Toxicol 25:456–467

Saris NE, Skulskii IA, Savina MV et al (1981) Mechanism of

mitochondrial transport of thallous ions. J Bioenerg Biomembr

13:51–59

Wojtovich AP, Williams DM, Karcz MK et al (2010) A novel

mitochondrial K(ATP) channel assay. Circ Res 106:

1190–1196

Zierold K (2000) Heavy metal cytotoxicity studied by electron

probe X-ray microanalysis of cultured rat hepatocytes.

Toxicol In Vitro 14:557–563

Thallium, Physical and ChemicalProperties

Fathi Habashi

Department of Mining, Metallurgical, and Materials

Engineering, Laval University, Quebec City, Canada

Thallium is a silvery white metal, considered a less

typical metal because when it loses its outermost elec-

trons it will not achieve the inert gas electronic

structure. It occurs as a trace element in pyrite, and is

extracted as a by-product of roasting this mineral for

the production of sulfuric acid. Thallium can also be

obtained from the smelting of lead and zinc sulfide

ores. The fresh surface of the metal has a bluish-white

luster. In many of its physical properties, thallium

resembles its neighbor, lead. It exists in two allotropic

forms: a-thallium, hexagonal close-packed, stable at

room temperature; and b-thallium, body-centered

cubic, stable above 226�C. A volume increase of

3.23% takes place on solidification.

Thallium and its compounds are extremely

toxic. The odorless and tasteless thallium sulfate

was once widely used as rat poison and ant killer.

Thallium (I) sulfide’s electrical conductivity

changes with exposure to infrared light therefore

making this compound useful in photoresistors.

Thallium selenide has been used in a bolometer

for infrared detection.

Physical Properties

Atomic number 81

Atomic weight 204.38

Relative abundance in Earth’s crust, % 3 � 10�5

Density, g cm�3 11.85

Melting point, �C 303

Boiling point, �C 1,473

Atomic radius, pm 170

Heat of fusion, kJ mol�1 4.14

Heat of vaporization, kJ mol�1 165

Molar heat capacity, J mol�1 K�1 26.32

Electrical resistivity at 20�C, mO m 0.18

Thermal conductivity, W m�1 K�1 46.1

Thermal expansion at 25�C, mm m�1 K�1 29.9

Young’s modulus, GPa 8

(continued)

T 2202 Thallium, Physical and Chemical Properties

Thallium, Effects on Mitochondria

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