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

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

Transmiterea i procesarea
semnalului n sistemul nervos
I. Date generale

SNC - 1011 neuroni;

- 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
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

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
AGONITI
ANTAGONITI

E
Celul

glial

Sinaps excitatorie
Sinaps inhibitorie

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 HIPOFIZARE

ACTH, B-endorfin, A-MSH, Prolactin,

LH, GH, TSH

PEPTIDE GASTROINTESTINALE

VIP, CCK, Gastrin, Neurotensin, MetEnkefalin, 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

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

Muscarinici (M)
Ag.muscarina, pilocarpina
Atg. atropina

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

nicotinici
neuronali
2-10

Ag.oxotremorina
Atg. propilbenzilcolina

muscarinici
M1-5

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

I.Distribuia receptorilor colinergici

Receptorii nicotinici musculari embrionari

- pe toat suprfaa fibrei musculare
neinervat sau denervat
- au o rat mare a turnover-lui
Receptorii nicotinici musculari joncionali
- la nivelul jonciunii neuromusculare
- au o rat mic a turnover-lui

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

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)

Sinapsa Colinergica
Transportor
Transportor
vezicular de ACh
Transportor
de colina

Muscarinici
carbachol
edrofoniu
Nicotinici musc.
suxametoniu

ACh

Nicotinici nn.
lobelina

vesamicol

Muscarinici
atropina
Nicotinici musc.
D-tubocurarina

ACh
ChAT

Colina

ACh

Nicotinici nn.
hexametoniu

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

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

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 setshifting 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 histaminergicihipotalamici
Rol-comportament

Modularea transmiterii
semnalului

Componenta trigger si de conducere

Canale de Na+ voltaj- dependente

Modularea activitii
receptor

Gk

PKC
activ

PLC

PKC
inactiv
DAG

Ptdins(4,5)P2

Na+

RACK

[Ca2+]

Inhibarea C Na
incetinirea inactivrii

Na1.8- PGE2 AMPC,

efect opus
TTX rezistent
Ali modulatori

Muscarina Ach-PLC
Dopamina,D1,AMPc,PKA
Cocaina efectul DA
Defosforilare
Fosfataza 1,2a
Calcineurina

Transmiterea sinaptic
electric

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.
Particulariti functionale:
-mecanism molecular
-sens, durat
-control
-voltaj membranar
-Ca, pH,

Transmitere efaptic

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