11/4/2013

Transmiterea i procesarea semnalului n sistemul nervos

I.Transmiterea sinaptic Transmiterea sinaptic chimic Transmiterea sinaptic electric II. Transmiterea nonsinaptic Transmiterea hormonal Transmiterea auto- paracrin Transmiterea efaptic

Transmiterea sinaptic chimic

11/4/2013

Transmiterea i procesarea semnalului n sistemul nervos

I. Date generale SNC - 1011 neuroni; - 1000 sinapse/neuron - neuron=microprocesor ? - alte mecanisme de comunicare

Transmiterea i procesarea semnalului n sistemul nervos

Repere istorice L.Galvani- electricitatea animal 1797 A.Volta-bateria electric 1800 H.C.Oersted-electromagnetism 1820

11/4/2013

Transmiterea i procesarea semnalului n sistemul nervos

Repere istorice Ch. Sherrington 1897, Sinapsa Otto Loewi-1920- Ach Cole K. S i Curtis.H -1939 impedana electric, giant axon Hodkin A.L. & Huxley A.F.1939,PA/Na

Sinapsa chimic
Segment presinaptic
AGONITI ANTAGONITI

E
Celul glial Sinaps excitatorie Sinaps inhibitorie

Segment postsinaptic

11/4/2013

Neurotransmitori cu molecul mic i enzimele lor de biosintez

Neurotransmitor ACETIL COLIN AMINE BIOGENE Dopamin Epinefrin Norepinefrin Serotonin Histamin AMINOACIZI GABA Glutamat Glicin Glutamat decarboxilaz Specificitate probabil Enzime din metabolismul general Enzime din metabolismul general Cale specific nedeterminat Cale specific nedeterminat Tirozin hidroxilaz Tirozin hidroxilaz i dopamin b hidroxilaz Tirozin hidroxilaz i dopamin b hidroxilaz Triptofan hidroxilaz Histidin decarboxilaz Specific Specific Specificitate incert Specific Enzime Colin acetiltransferaz Activitate Specific

Peptide cerebrale neuroactive clasificate dup localizarea tisular

Categoria HORMONI ELIBERATORI HIPOTALAMICI HORMONI NEUROHIPOFIZARI PEPTIDE HIPOFIZARE Peptide TRH, GnRH, Somatostatin, CRH, GH-RH Vasopresin, Oxitocin ACTH, B-endorfin, A-MSH, Prolactin, LH, GH, TSH VIP, CCK, Gastrin, Neurotensin, MetEnkefalin, Leu-Enkefalin, SP, Insulin, Glucagon, Bombezin, Secretin, SST, TRH, Motilin PAN Angiotensina II, Bradikinin, Calcitonin, CGRP, NPYY, Galanin, Substana K (Neurokinina A), Peptide de somn

PEPTIDE GASTROINTESTINALE

PEPTIDE CARDIACE

ALTELE

11/4/2013

Sinapsa colinergic

Receptori colinergici Nicotinici Ag.nicotina Atg. d-tubocurarina Muscarinici Ag.muscarina, pilocarpina Atg. atropina Ag.oxotremorina Atg. propilbenzilcolina

Nicotinici musculari Ag.feniltrimetilamoniu Atg. d-tubocurarina embrionar (1)2 jonctional (1)2

Nicotinici neuronali Ag.dimetilfenilpiperazina citisina Atg. trimetafan, bungarotoxin nicotinici neuronali 2-5 nicotinici neuronali 2-10

muscarinici M1-5

11/4/2013

R. MUSCARINICI

Muscarinici M1 pirenzepin Muscarinici M2 metoctramin Muscarinici M3 hexahidrosiladifenidol Muscarinici M4 himbacin Muscarinici M5 ?

Distribuia receptorilor colinergici I. Distribuia periferic - m.scheletic (N) - s n v (N+M) II. Distribuia central SNC (N+M) III. Alte roluri orgs. unicelulare orgs. pluricelulare dezvoltare difereniere

11/4/2013

I.Distribuia receptorilor colinergici Receptorii nicotinici musculari embrionari - pe toat suprfaa fibrei musculare neinervat sau denervat - au o rat mare a turnoverlui Receptorii nicotinici musculari joncionali - la nivelul jonciunii neuromusculare - au o rat mic a turnoverlui

I.Distribuia receptorilor colinergici Receptorii nicotinici neuronali - sp.i psp.din creasta neural, au proprieti identice - gg. postsinp. sp.,psp. i MS. Receptorii muscarinici neuronali - postgg.psp.- m.n.visceral, miocard glande secretorii - postgg.sp.- piloerecie, sudoraie

11/4/2013

II.Distribuia receptorilor colinergici -interneuronilor-corpul striat- controlul motor extrapiramidal i memorie -neuronilor de proiecie: din nc.bazali,conectati cu hipocampusul bulbul olfactiv i cortex.(Meynert- b. Alz. -din tr.cerebral, conectati cu talamusul, nc. interpeduncular,coliculii. sup - cel. Renshaw

Sistemul Colinergic (Neurochemistry of Consciousness.

Neurotransmitters in mind by Elaine Perry,Heather Ashton, Allan Young. John Benjamins BV. 2002)

11/4/2013

Sinapsa Colinergica
Transportor Transportor vezicular de ACh Transportor de colina

Muscarinici carbachol edrofoniu Nicotinici musc. suxametoniu Nicotinici nn. lobelina Muscarinici atropina Nicotinici musc. D-tubocurarina Nicotinici nn. hexametoniu

ACh

vesamicol
ACh ChAT

ACh

Colina AcCoA hemicolinium

AChE
ACh Ach

Colina + Ac Colina + Acfizostigmina

Sindr. M.Gravis...

Trasportor de colina (ChT)

- 13 segmente transmembranare - grad mare de conservare filogenetic - in alte esuturi, (Km=10-100 mol/L) - in neuron, Na dependent, situsuri de fosforilare, (Km= 1-5 mol/L) - co-localizat n membr. vezicular cu VAchT i n membrana sinaptic

11/4/2013

Trasportor de colina (ChT)

- blocarea endocitozei colinei - nr. i activitii ChT din membrana sinaptic - stimularea sintezei i elib. ACh - nr. i activitii ChT din membrana sinaptic - captarea Ch = factor de control al biosintezei i eliberrii ACh - tratamentul cu hemicolin

Transportor vezicular de acetilcolina (VAChT)

- 12 segmente transmembranare - gena localizat pe Cr.X in apropierea genei de sinteza a ChAT - este un antiporter H+ / ACh, ATP depentent - este inhibat selectiv de vesamicol

10

11/4/2013

Acetilcolinesteraza (AChE)
-Este un important factor de control al transmiterii sinaptice - animale knock out prezinta un tremor continuu, dezvoltare deficitar, disfuncii neurologice -Inhibitori AChE: sarinul, compui organofosforici induc fibrilaii musculare, blocarea activitii musculare

Acetilcolinesteraza (AChE)
-succinilcolina blocant muscular competitiv - miorelaxant - anticolinesteraze - tratament pentru miastenia gravis, B.Alzhaimer -inhibitori reversibili: edrofonium, galamina

11

11/4/2013

sinapsa glutamatergic

Sinapsa glutamatergica

12

11/4/2013

Transportori sinaptici

Sinapsa GABAergic

13

11/4/2013

Benzodiazepines Nonbenzodiazepine (Zolpidem) Barbiturice Methaqualone Baclofen Muscimol Progabide Tiagabine Bicuculline Metrazol Flumazenil

Sinapse cu amine biogene

Adrenergice Noradrenergice Dopaminergice Serotoninergice Histaminergice

14

11/4/2013

Sistemul dopaminergic

Dopamine transporters in the cortex are concentrated in cingulate and medial prefrontal regions.While cholinergic and noradrenergic systems are said to be involved in low level aspects of attention (e.g. Attentional orienting), the dopaminergic system contributes to motivated behaviours and is said to be associated with more executive aspects of attention such as attentional setshifting or working memory. It has recently been suggested that dopamine rather than signalling pleasure may function to highlight significant stimuli

15

11/4/2013

Sistemul Dopaminergic (Neurochemistry of Consciousness.

Neurotransmitters in mind by Elaine Perry,Heather Ashton, Allan Young. John Benjamins BV. 2002)

Sinapsa Serotoninergic
Rapport, Green and Page 1948-serotonin - Esparmer enteramin - Twarog and Page -1953- creier Rol- ritm circadian, emoie, depresie, anxietate, ef. vegetative

16

11/4/2013

Sinapsa Histaminergic Neuroni histaminergicihipotalamici Rol-comportament

Transmiterea i procesarea semnalului n sistemul nervos

II. Transmiterea nonsinaptic Transmiterea hormonal Transmiterea auto- paracrin Transmiterea efaptic

17

11/4/2013

Un model tridimensional al sinapsei electrice: A. Seciune prin sinaps. Fiecare din cele dou membrane conine cte o jumtate din canalul sinaptic. B.Conformaia conexonului variaz cu starea nchis/deschis.

Transmitere efaptic

18

11/4/2013

Myoclonus of peripheral origin: two case reports. Tyvaert L, Krystkowiak P, Cassim F, Houdayer E, Kreisler A, Deste A, Defebvre L. Mov Disord. 2009 Jan 30;24(2):274-7

Bilateral processing in chemical synapses with electrical 'ephaptic' feedback: a theoretical model. Savtchenko LP. Math Biosci. 2007 May;207(1):113-37. Epub 2006 Oct 7.PMID: 17112549

Rhythmic neuronal discharge in the medulla and spinal cord of fetal rats in the absence of synaptic transmission. Ren J, Momose-Sato Y, Sato K, Greer JJ. J Neurophysiol. 2006 Jan;95(1):527-34. Epub 2005 Sep 7

Neuron presinaptic Axon hillock

+ + + + + + + +

Neuron presinaptic

Neuron postsinaptic

19

11/4/2013

Modularea transmiterii semnalului

Componenta trigger si de conducere

20

11/4/2013

Canale de Na+ voltaj- dependente

Modularea activitii
receptor RACK Na+

Gk PLC

PKC activ PKC inactiv

Inhibarea C Na incetinirea inactivrii

Na1.8- PGE2 AMPC, efect opus TTX rezistent

Ali modulatori

DAG

Muscarina Ach-PLC Dopamina,D1,AMPc,PKA

Ptdins(4,5)P2

[Ca2+]

Cocaina efectul DA Defosforilare Fosfataza 1,2a Calcineurina

21