10/26/2012

Transmiterea i procesarea
semnalului n sistemul nervos
I.Transmiterea sinaptic
Transmiterea sinaptic chimic
Transmiterea sinaptic electric
II. Transmiterea nonsinaptic
Transmiterea
T
it
h
hormonal
l
Transmiterea auto- paracrin
Transmiterea efaptic

Transmiterea sinaptic
chimic

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Transmiterea i procesarea
semnalului n sistemul nervos

I. Date generale
SNC - 1011 neuroni;

- 1000 sinapse/neuron
- neuron=microprocesor ?
- alte
lt mecanisme
i
de
d comunicare
i

Transmiterea i procesarea
semnalului n sistemul nervos
Repere istorice
L Galvani electricitatea animal 1797
L.GalvaniA.Volta-bateria electric 1800
H C Oersted electromagnetism 1820
H.C.Oersted-electromagnetism

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Transmiterea i procesarea
semnalului n sistemul nervos
Repere istorice
Ch. Sherrington 1897, Sinapsa
Otto Loewi-1920- Ach
Cole
C
l K.
K S ii Curtis.H
C ti H -1939
1939
impedana electric, giant axon
Hodkin A.L. & Huxley A.F.1939,PA/Na

Sinapsa chimic
Segment
presinaptic
AGONITI

E
Celul
glial

ANTAGONITI

Sinaps excitatorie
Sinaps inhibitorie

Segment
postsinaptic

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Neurotransmitori cu molecul mic i enzimele lor de

biosintez
Neurotransmi
Neurot
ransmitor
tor

Enzime

Activitate

ACETIL COLIN

Colin acetiltransferaz

Specific

D
Dopamin
i

Tirozin
Ti
i hid
hidroxilaz
il

Specific
S
ifi

Epinefrin

Tirozin hidroxilaz i
dopamin b hidroxilaz

Norepinefrin

Tirozin hidroxilaz i
dopamin b hidroxilaz

Specific

Serotonin

Triptofan hidroxilaz

Specific

Histamin

Histidin decarboxilaz

Specificitate incert

AMINE BIOGENE

AMINOACIZI
GABA

Glutamat decarboxilaz Specificitate probabil

Glutamat

Enzime din
metabolismul general

Cale specific
nedeterminat

Glicin

Enzime din
metabolismul general

Cale specific
nedeterminat

Peptide cerebrale neuroactive

clasificate dup localizarea tisular
Categoria

Peptide

HORMONI ELIBERATORI
HIPOTALAMICI

TRH, GnRH, Somatostatin, CRH, GHGH-RH

HORMONI NEUROHIPOFIZARI

Vasopresin, Oxitocin

PEPTIDE HIPOFIZARE

ACTH, BB-endorfin, A
A--MSH, Prolactin,
LH, GH, TSH

PEPTIDE GASTROINTESTINALE

VIP, CCK, Gastrin, Neurotensin, MetMetEnkefalin, LeuLeu-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

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Sinapsa colinergic

Receptori colinergici
Nicotinici
Ag.nicotina
Atg. d-tubocurarina

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

Muscarinici
Ag.muscarina, pilocarpina
Atg. atropina

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

nicotinici
neuronali
li
2-10

Ag.oxotremorina
Atg. propilbenzilcolina

muscarinici
M1-5

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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

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I.Distribuia receptorilor colinergici

Receptorii nicotinici musculari embrionari
- pe toat
t t suprfaa
f fibrei
fib i musculare
l
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
i i identice
id i
- gg. postsinp. sp.,psp. i MS.
Receptorii muscarinici neuronali
postgg psp - m.n.visceral,
m n visceral miocard
- postgg.psp.
glande secretorii
- postgg.sp.- piloerecie, sudoraie

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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)

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Sinapsa Colinergica
Transportor
Transportor
vezicular de ACh
Transportor
de colina

ACh

Nicotinici musc.
suxametoniu
Nicotinici nn.
lobelina

vesamicol

Muscarinici
atropina
Nicotinici musc.
D-tubocurarina

ACh
ChAT

Colina

ACh

Nicotinici nn.
hexametoniu

AcCoA

AChE
ACh
Ach

Muscarinici
carbachol
edrofoniu

fizostigmina

hemicolinium
Colina
+ Ac
Colina
+ Ac-

M.Gravis ?...
BNCh 188

PPSI poate fi mediat de DOPA i NA eliberate de

interneuroni sub aciunea Ach, i poate fi blocat de
antagoniti alfa adrenergici. PPSI poate avea
parametrii dinamici asemntori PPSE

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Trasportor de colina (ChT)

- 13 segmente transmembranare
- grad mare de conservare
filogenetic
- in alte esuturi, (Km=10-100 mol/L)
- in neuron
neuron, Na dependent,
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

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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
I hibit i AChE
AChE: sarinul,
i l compuii
organofosforici induc fibrilaii
musculare, blocarea activitii musculare

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

sinapsa noradrenergic

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Sinapsa noradrenergica

Subtipuri de receptori 1-adrenergici

1A
Aminoacizi
430-476
Cromosom
8
Cale efectoare Ca2+, PKC
Distributie

inim,
inim ficat,
ficat
cerebellum,
cortex cerebral,
vase sanguine

1B
515
5
Ca2+, PKC

1D
560
20
Ca2+, PKC

splin, rinichi,
splin
rinichi aorta,
aorta
creier fetal
cortex cerebral
vase sang

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Subtipuri de receptori 2-adrenergici

2A

2B

Aminoacizi
450
450
Cromosom
10
2
Cale efectoare cAMP
cAMP
Distribution
pancreas,
ficat,
intestin subire, talamus
locus ceruleus
hipocampus

2C
461
4
cAMP
inim,plmn
aorta, hipocampus
bulb olfactiv,

Subtipuri de receptori -adrenergici

1

Aminoacizi

477

413

Cromosom

10

Cale efectoare

cAMP

cAMP

Distributie

3
402/408
8
cAMP

inim, rinichi,
plmn,ficat
creier,
cortex cerebral,
cerebral cerebellum,
cerebellum
esut adipos
hipotalamus
hipocampus,
cortex cerebral,
muschi neted,
bulb olfactiv

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Sistemul Noradrenergic (Neurochemistry of

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

Caracteristici ale oarecilor knockout

pentru receptori catecolaminergici
Knockout

Fenotip

Receptor adrenergic 1A

Scderea presiunii arteriale

Receptor adrenergic 1B

Scderea presiunii arteriale i a rspunsului la

stimulenii SNC

Receptor adrenergic 1D

Scderea presiunii arteriale

Receptor adrenergic 2A

Creterea activitii simpatice, tahicardie

Receptor adrenergic 2B

Scderea rspunsului vasoconstrictor la

agonitii 2

R
Receptor
t adrenergic
d
i 2C

F un fenotip
Fr
f
ti evident
id t

Receptor adrenergic 1

Majoritatea mor prenatal

Receptor adrenergic 2

Modificri de tonus vascular i de metabolism

energetic n stres

Receptor adrenergic 3

Modificarea concentraiilor de leptin i insulin

dup tratamentul cu agoniti

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Modularea chimic
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

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10/26/2012

Sistemul Dopaminergic (Neurochemistry of Consciousness.

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

sinapsa glutamatergic

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Sinapsa glutamatergica

Transportori sinaptici

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sinapsa GABAergic

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

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10/26/2012

Transmiterea i procesarea
semnalului n sistemul
nervos
II. Transmiterea nonsinaptic
Transmiterea hormonal
Transmiterea auto- paracrin
Transmiterea efaptic

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.

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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):2747

Bilateral processing in chemical synapses with electrical

'ephaptic' feedback: a theoretical model. Savtchenko LP.
Math Biosci. 2007 May;207(1):11337. 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,
MomoseSato Y, Sato K, Greer JJ. J Neurophysiol. 2006
Jan;95(1):52734. Epub 2005 Sep 7

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Neuron presinaptic
Axon
hillock
+
+
+
+

+
+
+
+

Neuron
presinaptic

Neuron postsinaptic

Modularea transmiterii
semnalului

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Componenta trigger
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

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