Transmiterea i procesarea semnalului n sistemul nervos

II. Transmiterea nonsinaptic

Transmiterea efaptic

Transmiterea auto- paracrin

Transmiterea hormonal

I.Transmiterea sinaptic

Transmiterea sinaptic electric

Transmiterea sinaptic chimic

My hope is that this textbook conveys the majesty of human body and its many functions and that it stimulates students to study physiology throughout theyr careers. The great beauty of physiology is that integrates the individual function of all the bodys different cells, tissues and organs into a functional whole, the human body.

Textbook of Medical Physiology Guyton and Hall. 2011

I. Date generale

SNC - 1011 neuroni;

Transmiterea i procesarea semnalului n sistemul nervos

- 1000 sinapse/neuron

- neuron=microprocesor ?

Transmiterea i procesarea semnalului n sistemul nervos

Repere istorice

L.Galvani- electricitatea animal 1797

A.Volta-bateria electric 1800

H.C.Oersted-electromagnetism 1820

Transmiterea i procesarea semnalului n sistemul nervos

Repere istorice

Otto Loewi-1920- Ach

Cole K. S i Curtis.H -1939impedana electric, giant axon

Ch. Sherrington 1897, Sinapsa

Hodkin A.L. & Huxley A.F.1939,PA/Na

Transmiterea sinaptic chimic

Canale-receptor controlate chimic

- ionotrope- NT-se cupleaz cu

receptorul canal

- metabotrope- NT-se cupleaz cu

receptorul postsinaptic care declaneaz mesagerul secund ce controleaz canalul ionic

-optogenetic- biofotoni

Sinapsa chimic

Segment

presinaptic

E

AGONITI

ANTAGONITI

Sinaps excitatorie

Sinaps inhibitorie

Celul

glial

Segment

postsinaptic

Neurotransmitori cu molecul mic i enzimele lor de biosintez

Neurotransmitor Enzime Activitate

ACETIL COLIN Colin acetiltransferaz Specific

Dopamin Tirozin hidroxilaz Specific

Epinefrin Tirozin hidroxilaz i dopamin b hidroxilaz

Norepinefrin Tirozin hidroxilaz i dopamin b hidroxilaz

Specific

Serotonin Triptofan hidroxilaz Specific

Histamin Histidin decarboxilaz Specificitate incert

GABA Glutamat decarboxilaz Specificitate probabil

Glutamat Enzime din metab. gen Cale specific nedet.

Glicin

Oxid Nitric

Enzime din metab. gen Cale specific nedet.

Peptide cerebrale neuroactive clasificate dup localizarea tisular

Categoria Peptide

HORMONI ELIBERATORI HIPOTALAMICI

TRH, GnRH, Somatostatin, CRH, GH-RH

HORMONI NEUROHIPOFIZARI Vasopresin, Oxitocin

PEPTIDE HIPOFIZAREACTH, B-endorfin, A-MSH, Prolactin, LH, GH, TSH

PEPTIDE GASTROINTESTINALE

VIP, CCK, Gastrin, Neurotensin, Met-Enkefalin, Leu-Enkefalin, SP, Insulin, Glucagon, Bombezin, Secretin, SST, TRH, Motilin

PEPTIDE CARDIACE PAN

ALTELE

Angiotensina II, Bradikinin, Calcitonin, CGRP, NPYY, Galanin, Substana K (Neurokinina A), Peptide de somn

Sinapsa colinergic

Receptori colinergici.

Nicotinici (N)

Ag.nicotina

Atg. d-tubocurarina

Muscarinici (M)

Ag.muscarina, pilocarpina

Atg. atropina

Ag.oxotremorina

Atg. propilbenzilcolina

Nicotinici musculari

Ag.feniltrimetilamoniu

Atg. d-tubocurarina

Nicotinici neuronali

Ag.dimetilfenilpiperazina

citisina

Atg. trimetafan, bungarotoxin

embrionar

(1)2

jonctional

(1)2

nicotinici

neuronali

2-10

nicotinici

neuronali

2-5

muscarinici

M1-5

R. MUSCARINICI

Muscarinici M1

pirenzepin

Muscarinici M2

metoctramin

Muscarinici M3

hexahidrosiladifenidol

Muscarinici M4

himbacin

Muscarinici M5

?

I. Distribuia periferic

- m.scheletic (N)

- s n v (N+M)

II. Distribuia central SNC (N+M)

Distribuia receptorilor colinergici

III. Alte roluri

orgs. unicelulare orgs. pluricelulare

dezvoltare

difereniere

Receptorii nicotinici musculari embrionari

- pe toat suprfaa fibrei musculare

neinervat sau denervat

- au o rat mare a turnover-lui

I.Distribuia receptorilor colinergici

Receptorii nicotinici musculari joncionali

- la nivelul jonciunii neuromusculare

- au o rat mic a turnover-lui

Receptorii nicotinici neuronali

I.Distribuia receptorilor colinergici

Receptorii muscarinici neuronali

- gg. postsinp. sp.,psp. i MS.

- sp.i psp.din creasta neural,

au proprieti identice

- postgg.psp.- m.n.visceral, miocard

glande secretorii

- postgg.sp.- piloerecie, sudoraie

II.Distribuia receptorilor colinergici

- cel. Renshaw

-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

Sistemul Colinergic (Neurochemistry of Consciousness. Neurotransmitters in mind by Elaine Perry,Heather Ashton, Allan

Young. John Benjamins BV. 2002)

Transportor

de colina

Transportor

Transportor

vezicular de ACh

Muscarinici

carbachol

edrofoniu

Muscarinici

atropina

Sinapsa Colinergica

Sindr. M.Gravis...

ACh

ACh

fizostigmina

vesamicol

hemicolinium

AChAch

AChE

Colina + Ac-Colina + Ac -

ACh

Colina

AcCoA

ChAT

Nicotinici nn.

lobelina

Nicotinici musc.

suxametoniu

Nicotinici nn.

hexametoniu

Nicotinici musc.

D-tubocurarina

Trasportor de colina (ChT)

- 13 segmente transmembranare

- grad mare de conservare

filogenetic

- in neuron, Na dependent, situsuri de

fosforilare, (Km= 1-5 mol/L)

- in alte esuturi, (Km=10-100 mol/L)

- co-localizat n membr. vezicular

cu VAchT i n membrana sinaptic

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 inhibat selectiv de vesamicol

- este un antiporter H+ / ACh, ATP

depentent

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

sinapsa glutamatergic

Sinapsa glutamatergica

Transportori sinaptici

Sinapsa GABAergic

Benzodiazepines

Nonbenzodiazepine

(Zolpidem)

Barbiturice

Methaqualone

Baclofen

Muscimol

Progabide

Tiagabine

Bicuculline

Metrazol

Flumazenil

Sinapse cu amine biogene

Adrenergice

Noradrenergice

Dopaminergice

Serotoninergice

Histaminergice

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 set-

shifting or working memory. It has

recently been suggested that dopamine

rather than signalling pleasure may

function to highlight significant stimuli

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

Sinapsa Histaminergic

Neuroni histaminergici-hipotalamici

Rol-comportament

Modularea transmiterii

semnalului

Componenta trigger si de conducere

Canale de Na+ voltaj- dependenteModularea activitii

Na+receptor

Gk

PLC

PKC

activ

[Ca2+]

PKC

inactiv

RACK

P

Ptdins(4,5)P2

DAG

Inhibarea C Na incetinirea inactivrii

Dopamina,D1,AMPc,PKA

Ali modulatori

Muscarina Ach-PLC

Cocaina efectul DA

Fosfataza 1,2aCalcineurina

Defosforilare

Na1.8- PGE2 AMPC,

efect opus

TTX rezistent

Transmiterea sinaptic electric

Un model tridimensionalal 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.

Particulariti functionale:-mecanism molecular-sens, durat-control

-voltaj membranar-Ca, pH,

Transmitere efaptic

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

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

++++

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Axon hillock

Neuron presinaptic

Neuron postsinaptic

Neuron presinaptic