NEUROTRANSMITER ngaji

7/30/2019 NEUROTRANSMITER ngaji

1/60


2/60

Stimulus yang datang dari lingkungan, baik berupacahaya, suara, tekanan, sentuhan, suhu, ataupunstimulus yang lain, akan diterima oleh reseptor .Reseptor adalah bagian dari sel saraf yang terdapatpada organ pengindera. Di dalam reseptor, stimulusyg datang akan diubah dalam bentuk kodeinformasi. Kode informasi tersebut berupaperubahan elektrokimiawi pada neuron dan disebut

sebagai impuls saraf .Impuls saraf inilah yang oleh neuron diteruskan keotak untuk dipersepsi. Hasil persepsi otak kemudianakan dihantarkan kembali menuju efektor .


3/60

Efektor adalah sel atau organ yangmenghasilkan tanggapan terhadaprangsangan/stimulus, seperti otot, kelenjar,atau sel target sehingga terjadigerakan/aktivitas.

Penghantaran impuls saraf tersebut terjadimelalui serabut akson dan sinapsis .


4/60


5/60


6/60

Penghantaran impuls, baik berupa rangsanganataupun tanggapan melalui serabut akson,terjadi karena adanya perbedaan potensial listrikantara bagian luar dan bagian dalam sel.

Pada waktu sel saraf beristirahat ( polarized ),kutub positif terdapat di bagian luar dan kutubnegatif terdapat di bagian dalam sel saraf.

Diperkirakan bahwa rangsangan (stimulus) padaindra menyebabkan terjadinya pembalikanperbedaan potensial listrik sesaat.


7/60

Extrasel lebih banyak mengandung ion natriumsehingga muatan lebih positif, sebaliknya intrasel

lebih banyak mengandung ion kalium sehinggamuatannya lebih negatif.Sifat membran sel saraf relatif impermeable terhadap kedua ion.


8/60

Stimulus yang datang menyebabkan terjadinya pembalikanpotensial listrik. Ion natrium secara cepat berpindah kebagian dalam sel saraf sehingga muatan bagian luar menjadilebih negatif dibanding bagian dalam sel saraf.

Dalam keadaan ini, sel saraf dikatakan mengalamidepolarisasi .

Pada tempat perangsangan (datangnya stimulus)terbentuklah potensial aksi . Jika stimulus cukup kuat,potensial aksi akan dialirkan secara cepat ke sepanjangmembran serabut akson.


9/60

Kecepatan perjalanan gelombang perbedaan

potensial pada serabut akson bervariasi antara 1- 120 m per detik, tergantung pada diameter akson dan ada atau tidaknya selubung mielin .

Bila impuls telah lewat, maka untuk sementaraserabut saraf tidak dilalui oleh impuls yang lain.Ini berarti bahwa serabut saraf mengalamiperubahan potensial, kembali seperti semula(potensial istirahat).

Untuk dapat berfungsi kembali diperlukan waktu1/500 sampai 1/1000 detik.


10/60

Stimulasi yang kurang kuat atau di bawah ambang

( threshold ) tidak akan menghasilkan impuls yangdapat merubah potensial listrik. Sebaliknya, bilakekuatan stimulus di atas ambang maka impulsakan dihantarkan sampai ke ujung akson.

Stimulasi yang kuat dapat menimbulkan jumlahimpuls yang lebih besar pada periode waktutertentu daripada impuls yang lemah.

Proses pengubahan stimulus menjadi impulsmengikuti hukum all or none (semua atau tidaksama sekali).


11/60

Muncul tidaknya suatu impuls, dapat terjadi karenadua kemungkinan, yaitu:1. Penjumlahan temporal 2. Penjumlahan spasial

Jenis neuron berdasarkan kemampuannyamenghantarkan impuls

1. Neuron eksitatoris2. Neuron inhibitoris


12/60

Impuls yang telah sampai di bagian terujung dariserabut akson ( terminal akson ) akan disampaikanke neuron berikutnya.

Titik temu antara terminal akson salah satuneuron dengan neuron lain dinamakan sinapsis . Setiap terminal akson membengkak membentuktonjolan sinapsis. Di dalam sitoplasma tonjolan

sinapsis terdapat struktur kumpulan membrankecil berisi neurotransmitter; yang disebutvesikula sinapsis .


13/60

Neuron yang berakhir pada tonjolan sinapsis

disebut neuron pra-sinapsis . Membran ujungdendrit dari sel berikutnya yang membentuksinapsis disebut post-sinapsis .Bila impuls sampai pada ujung neuron, maka

vesikula bergerak dan melebur dengan membranpra-sinapsis. Kemudian vesikula akanmelepaskan neurotransmitter .Neurontransmitter adalah suatu zat kimia yang

diproduksi oleh n pra-sinapsis dan dapatmenyeberangkan impuls dari n pra-sinapsismenuju ke n post-sinapsis.


14/60

Neurotransmiter merupakan cara komunikasi antar neuron. Setiap neuron melepaskan satu transmitter.Zat zat kimia ini menyebabkan perubahanpermeabilitas sel neuron, sehingga neuron menjadilebih kurang dapat menyalurkan impuls.Neurotransmiter yang dilepaskan oleh n pra-sinapsisakan berdifusi melewati celah sinapsis dan menempel

pada reseptor yang terdapat pada membran post-sinapsis .Menempelnya neurotransmiter pada reseptor menyebabkan timbulnya impuls pada neuron post-sinapsis .

Bila neurotransmiter sudah melaksanakan tugasnyamaka neurotransmiter akan diurai oleh enzim yangdihasilkan oleh membran post-sinapsis .


15/60


16/60


17/60

17


18/60

18

Neurotransmitters found in the nervous system

EXCITATORY

Acetylcholine AspartateDopamineHistamineNorepinephrineEpinephrineGlutamateSerotonin

INHIBITORYGABAGlycine


19/60

1. Asetilkolin yang terdapat di seluruh tubuh, kecualiotak.2. Dopamin yang terdapat di otak.

Dopamin berperan dalam mengendalikan fungsi

gerakan, konsentrasi, dan proses kecanduan.Kerusakan pada neuron dopaminergik menyebabkan:

1. Parkinson (akibat kekurangan dopamin)

2. Skizofrenia (akibat kelebihan dopamin)

3. Seretonin yang terdapat di otak.Seretonin dapat merangsang orang yang sedang tidur menjadi bermimpi.


20/60

In the cholinergic neurons acetylcholine is synthesizedfrom choline. This reaction is activated bycholineacetyltransferase

20

As soon as acetylcholine is synthesized,it is stored within synaptic vesicles .


21/60

Acetylcholin Synthese


22/60

Cholinergic pathways in the brain - basal forebrain, dorsolateral pons,medial septum.

muscular movement faciliatory effect REM sleep learning memories


23/60

Glutamat Synthese


24/60

GABA and Glycin Synthese


25/60


26/60


27/60

-this is not for torture-understanding synthesis can be important

for understanding drug action


28/60

Subtantia nigra andParkinson s disease

Mesocorticolimbicsystem andschizophrenia

Receptor specificity

Dopamine


29/60

Histidin

HistidinDecarboxylase

Histamin


30/60

Tyrosin

Tyramin

Octopamin

Tyrosin Decarboxylase

Tyramin -Hyroxylase


31/60

31

Other Neurotransmitters:

Neurotransmitter Derived from Enzyme

Histamine Histidine Histidinedecarboxylase

GABA ( -Aminobutyrate)

Glutamate Glutamatedecarboxylase

Nitric Oxide Arginine Nitric OxideSynthase


32/60

Neurotransmitter

Molecule Derived

From Site of Synthesis

Acetylcholine Choline CNS, parasympathetic nerves

Serotonin 5-Hydroxytryptamine (5-HT)

Tryptophan CNS, chromaffin cells of the gut, entericcells

GABA Glutamate CNS

Histamine Histidine hypothalamus

Epinephrine synthesis pathway

Tyrosine adrenal medulla, some CNS cells

Norpinephrine synthesis pathway

Tyrosine CNS, sympathetic nerves

Dopamine synthesis pathway

Tyrosine CNS

Nitric oxide, NO Arginine CNS, gastrointestinal tract

Summary:
http://www.indstate.edu/thcme/mwking/nerves.htmlhttp://www.indstate.edu/thcme/mwking/nerves.htmlhttp://www.indstate.edu/thcme/mwking/nerves.htmlhttp://www.indstate.edu/thcme/mwking/nerves.htmlhttp://www.indstate.edu/thcme/mwking/aminoacidderivatives.htmlhttp://www.indstate.edu/thcme/mwking/nerves.htmlhttp://www.indstate.edu/thcme/mwking/aminoacidderivatives.htmlhttp://www.indstate.edu/thcme/mwking/nerves.htmlhttp://www.indstate.edu/thcme/mwking/aminoacidderivatives.htmlhttp://www.indstate.edu/thcme/mwking/aminoacidderivatives.htmlhttp://www.indstate.edu/thcme/mwking/aminoacidderivatives.htmlhttp://www.indstate.edu/thcme/mwking/aminoacidderivatives.htmlhttp://www.indstate.edu/thcme/mwking/nerves.htmlhttp://www.indstate.edu/thcme/mwking/aminoacidderivatives.htmlhttp://www.indstate.edu/thcme/mwking/nerves.htmlhttp://www.indstate.edu/thcme/mwking/aminoacidderivatives.htmlhttp://www.indstate.edu/thcme/mwking/nerves.htmlhttp://www.indstate.edu/thcme/mwking/nerves.htmlhttp://www.indstate.edu/thcme/mwking/nerves.htmlhttp://www.indstate.edu/thcme/mwking/nerves.html


33/60

1. After being released into the synapse (the gapbetween nerve endings and receiver cells), dopaminebinds to receptors on the next neuron

2. The dopamine is either quickly reabsorbed or brokendown by the enzyme monoamine oxidase (MAO)

Dopamine s Normal Action

Based on Time , May 5,1997


34/60

Cocaine blocks thenormal absorption of dopamine. As a result,dopamine accumulatesin the synapse, whereis stimulates thereceiver cell.

Amphetaminesstimulate excessrelease of dopamine,overwhelming theprocesses of reuptakeand enzyme

breakdown.

Nicotine stimulates therelease of dopamine,while another substance in cigarettesmoke blocks theaction of MAO.

How Drug Affect Dopamine Levels

Based on Time , May 5, 1997


35/60

Nucleus basalis of Meynert


36/60

Largely unknown-Down s syndrome link -but strongly inherited forms account for only small

proportion-plaques seen in wide variety of disorders acquired by

disease (encephalitis, CJD) and accident (punch- drunk syndrome)


37/60

1. Cognitive enhancers -Acetylcholinesterase inhibitors to offset loss of cholinergic

neurons

2. NMDA antagonists-Memantine

-idea here is that part of problem in AD is that chronicrelease of glutamate prevents NMDA receptors fromworking properly


38/60


39/60

QuickTime and aTIFF (LZW) decompressor are need ed to see this picture.

Methamphetamine alters Dopamine transmissionin two ways:

1. Enters dopamine vesicles in axon terminal causingrelease of NT

2. Blocks dopamine transporters from pumping

dopamine back into the transmitting neuron

NIH Publication No. 00-4871

seattlepi.nwsource.com/ methamphetamines/


40/60

This causes neurons to fire more often thannormal resulting in a euphoric feeling.


41/60

1. After the drug wears off, dopamine levelsdrop, and the user crashes. The euphoricfeeling will not return until the user takesmore methamphetamine

2. Long-term use of methamphetaminecauses dopamine axons to wither anddie.

3. Note that cocaine also blocks dopamine transporters, thus it works in a similar manner.


42/60

Similar to methamphetamine and cocaine ,nicotine increases dopamine release in asynapse.However, the mechanism is slightly different.Nicotine binds to receptors on the presynapticneuron .


43/60

Nicotine binds to the presynaptic receptors exciting the neuron to fire moreaction potentials causing an increase indopamine release.Nicotine also affects neurons byincreasing the number of synapticvesicles released .


44/60

Alcohol has multiple effects on neurons. Italters neuron membranes, ion channels,enzymes, and receptors.

It binds directly to receptors for acetylcholine, serotonin, and gammaaminobutyric acid (GABA), and glutamate.We will focus on GABA and its receptor.


45/60

GABA is a neurotransmitter that has aninhibitory effect on neurons.When GABA attaches to its receptor on thepostsynaptic membrane, it allows Cl - ions to

pass into the neuron.This hyperpolarizes the postsynaptic neuron toinhibit transmission of an impulse.


46/60

When alcohol enters the brain, it binds to GABA receptors and amplifies the hyperpolarization effect of GABA .The neuron activity is further diminishedThis accounts for someof the sedative affects of alcohol

science.howstuffworks.com/ alcohol.htm


47/60

The brain goes through dynamic change duringadolescence, and alcohol can seriously damagelong- and short-term growth processes .Frontal lobe development and the refinement of pathways and connections continue until age 16, anda high rate of energy is used as the brain maturesuntil age 20.

Damage from alcohol at this time can be long-term and irreversible.

From AMA pub 9416


48/60

In addition, short-term or moderate drinkingimpairs learning and memory far more inyouth than adults.

Adolescents need only drink half as muchas adults to suffer the same negativeeffects.


49/60

Change in Neurotransmission Effect on Neurotransmitterrelease or availability Drug that acts this way

increase the number of impulses increased neurotransmitter release

nicotine, alcohol, opiates

release neurotransmitter fromvesicles with or without impulses

increased neurotransmitter release

amphetaminesmethamphetamines

release more neurotransmitter inresponse to an impulse

increased neurotransmitter release

nicotine

block reuptake more neurotransmitter present insynaptic cleft

cocaineamphetamine

produce less neurotransmitter less neurotransmitter in synapticcleft

probably does not work this way

prevent vesicles from releasingneurotransmitter

less neurotransmitter released No drug example

block receptor with another molecule

no change in the amount of neurotransmitter released, or

neurotransmitter cannot bind toits receptor on postsynaptic

neuron

LSDcaffeine

NIH Publication No. 00-4871


50/60

TERIMA KASIH


51/60


52/60

1)When the nerve impulse (Action potential) moves down thepresynaptic axon to the terminal bulb the change in the membraneaction potential causes the opening of voltage gated calcium channelsopen allowing Ca +2 ions to pass from the synaptic cleft into the axonbulb.

2) Within the bulb the increasein Ca +2 concentration causes thesynaptic vesicles that contain

acetylcholine to fuse with theaxonal membrane and openspilling their contents intothe synaptic cleft.

52


53/60

The postsynaptic membrane of the receptor dendrite has specific cholinergicreceptors toward which the neurotransmitter diffuses. Binding of acetylcholine trigger the opening of ion channels in the postsynapticmembrane initiating action potential that can pass in the next axon.

53

Acetylcholine receptors:Acetylcholine receptors are ion channels receptors

made of many subunits arranged in the form[(2)()()()].

When Acetylcholine is not bounded to thereceptors, the bulky hydrophobic leu side close thecentral channels preventing the diffusion of any ions.

Binding of two acetylcholine molecules to thereceptors will rotate the subunits in which the smaller polar residues will line the ion channel causing theinflux of Na+ into the cell and efflux of K+ resulting ina depolarization of the postsynaptic neuron and the

initiation of new action potential.


54/60

In order to ready the synapse for another impulses:1) The neurotransmitters, which are released from the synapticvesicles, are hydrolyzed by enzyme present in the synaptic cleftAcetylcholinestrase giving choline, which poorly binds toacetylcholine receptors.

Acetylcholine + H2O Choline + H+ acetate

2) The empty synaptic vesicles, which are returned to the axonalterminal bulb by endocytosis, must be filled with acetylecholine.

54

Acetylcholinestrase


55/60

Acetylcholinesterase (AchE) is an

enzyme, which hydrolyses theneurotransmitter acetylcholine. Theactive site of AChE is made up of twosubsites, both of which are critical tothe breakdown of ACh . The anionic siteserves to bind a molecule of ACh to theenzyme. Once the ACh is bound, thehydrolytic reaction occurs at a secondregion of the active site called theesteratic subsite. Here, the ester bondof ACh is broken, releasing acetate and

choline. Choline is then immediatelytaken up again by the high affinitycholine uptake system on thepresynaptic membrane.


56/60


57/60

Vertebraten Invertebraten

Acetylcholin Acetylcholin

GABA GABA

Glutamat Glutamat

Glycin

Biogene Amine Histamin Histamin

Serotonin Serotonin

Dopamin DopaminNoradrenalin

Adrenalin

(Noradrenalin)

Tyramin/Octopamin

Neuropeptide


58/60

Neurotransmitter Neuropeptide


59/60

1) First Step: Hydroxylation:In this step: the reaction involves the conversion of tyrosine, oxygen and tetrahydrobiopterin to dopa &dihydrobiopterin. This reaction is catalyzed by the

enzyme tyrosine hydroxylase . It is irreversible reaction.2) Second step: Decarboxylation: In this step: the dopa decaboxylase will catalyze thedecaoxylation of dopa to produce dopamine. The

deficiency of this enzyme can cause Parkinsonsdisease. It is irreversible reaction. The cofactor in thisreaction is the PLP (pyridoxal phosphate). In the nervecells that secrete dopamine as neurotransmitter thepathway ends at this step.

59


60/60

3) Third step: Hydroxylation:

This reaction is catalyzed by the enzyme dopamine -hydroxylase. The reactants include dopamine, O 2 andascorbate (vitamin C). The products are norepinephrine,water and dehydroascorbate. It is an irreversiblereaction). The end product in noradrenergic cells isnorepinephrine and the pathway ends her.

4) Forth step: Methylation:This reaction is catalyzed by phenylethanolamine N-methyltransferase. Norepinephrine and S-adenosylmethionin (ado-Met) form epinephrine and S-

Catecholamine Synthesis (Dopamine, Norepinephrine and Epinephrine).

NEUROTRANSMITER ngaji

Documents

Transcript of NEUROTRANSMITER ngaji