11/4/2013

1
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
Transmiterea sinaptic
chimic
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I. Date generale
SNC - 10
11
neuroni;
Transmiterea i procesarea
semnalului n sistemul nervos
- 1000 sinapse/neuron
- alte mecanisme de comunicare
- 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
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Transmiterea i procesarea
semnalului n sistemul nervos
Repere istorice
Otto Loewi-1920- Ach
Cole K. S i Curtis.H -1939
impedana electric, giant axon
Ch. Sherrington 1897, Sinapsa
Hodkin A.L. & Huxley A.F.1939,PA/Na
Sinapsa chimic
Segment
presinaptic
E
AGONITI
ANTAGONITI
Sinaps excitatorie
Sinaps inhibitorie
Celul
glial
Segment
postsinaptic
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Neurotransmitori cu molecul mic i enzimele lor de
biosintez
Neurotransmitor Enzime Activitate
ACETIL COLIN Colin acetiltransferaz Specific
AMINE BIOGENE
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
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, GH-RH
HORMONI NEUROHIPOFIZARI Vasopresin, Oxitocin
PEPTIDE HIPOFIZARE
ACTH, 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
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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
Nicotinici neuronali
Ag.dimetilfenilpiperazina
citisina
Atg. trimetafan, bungarotoxin
embrionar
(
1
)
2

jonctional
(
1
)
2

nicotinici
neuronali

2-10
nicotinici
neuronali

2-5
muscarinici
M
1-5
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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
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Receptorii nicotinici musculari embrionari
- pe toat suprfaa fibrei musculare
neinervat sau denervat
- au o rat mare a turnoverlui
I.Distribuia receptorilor colinergici
Receptorii nicotinici musculari joncionali
- la nivelul jonciunii neuromusculare
- au o rat mic a turnoverlui
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
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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)
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Transportor
de colina
Transportor
Transportor
vezicular de ACh
Muscarinici
carbachol
edrofoniu
Muscarinici
atropina
Sinapsa Colinergica
Sindr. M.Gravis...
ACh
ACh
fizostigmina
vesamicol
hemicolinium
ACh
Ach
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, (K
m
= 1-5 mol/L)
- in alte esuturi, (K
m
=10-100 mol/L)
- co-localizat n membr. vezicular
cu VAchT i n membrana sinaptic
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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
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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
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sinapsa glutamatergic
Sinapsa glutamatergica
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Transportori sinaptici
Sinapsa GABAergic
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Benzodiazepines
Nonbenzodiazepine
(Zolpidem)
Barbiturice
Methaqualone
Baclofen
Muscimol
Progabide
Tiagabine

Bicuculline
Metrazol
Flumazenil
Sinapse cu amine biogene
Adrenergice
Noradrenergice
Dopaminergice
Serotoninergice
Histaminergice
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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
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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
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Sinapsa Histaminergic
Neuroni histaminergici-
hipotalamici
Rol-comportament
Transmiterea i procesarea
semnalului n sistemul
nervos
II. Transmiterea nonsinaptic
Transmiterea efaptic
Transmiterea auto- paracrin
Transmiterea hormonal
11/4/2013
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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
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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
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Modularea transmiterii
semnalului
Componenta trigger si de conducere
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Canale de Na
+
voltaj- dependente
Modularea activitii
Na
+

receptor
Gk
PLC
PKC
activ
[Ca
2+
]
PKC
inactiv
RACK
P
Ptdins(4,5)P
2

DAG
Inhibarea C
Na

incetinirea inactivrii

Dopamina,D
1
,AMPc,PKA
Ali modulatori
Muscarina Ach-PLC
Cocaina efectul DA
Fosfataza 1,2a
Calcineurina
Defosforilare
Na1.8- PGE
2
AMPC,
efect opus
TTX rezistent