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I.Transmiterea sinaptic Transmiterea sinaptic chimic Transmiterea sinaptic electric II. Transmiterea nonsinaptic Transmiterea T it h hormonal l Transmiterea auto- paracrin Transmiterea efaptic
Sinapsa chimic
Segment presinaptic
AGONITI
E
Celul glial
ANTAGONITI
Segment postsinaptic
PEPTIDE GASTROINTESTINALE
PEPTIDE CARDIACE
ALTELE
Sinapsa colinergic
Receptori colinergici Nicotinici Ag.nicotina Atg. d-tubocurarina Muscarinici Ag.muscarina, pilocarpina Atg. atropina Ag.oxotremorina Atg. propilbenzilcolina
Nicotinici neuronali Ag.dimetilfenilpiperazina citisina Atg. trimetafan, bungarotoxin nicotinici neuronali li 2-5 nicotinici neuronali li 2-10
muscarinici M1-5
R. MUSCARINICI
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 t t suprfa f a 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 propriet 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
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 Nicotinici nn. lobelina Muscarinici atropina Nicotinici musc. D-tubocurarina Nicotinici nn. hexametoniu
ACh
vesamicol
ACh ChAT ACh
AChE
ACh Ach
M.Gravis ?...
BNCh 188
fizostigmina
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
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 compui organofosforici induc fibrilaii musculare, blocarea activitii musculare
Acetilcolinesteraza (AChE)
-succinilcolina blocant muscular competitiv - miorelaxant - anticolinesteraze i i - tratament pentru miastenia gravis, B.Alzhaimer -inhibitori reversibili: edrofonium, galamina
sinapsa noradrenergic
Sinapsa noradrenergica
Subtipuri de receptori 1-adrenergici 1A Aminoacizi 430-476 Cromosom 8 Cale efectoare Ca2+, PKC Distributie inim, ficat, ficat cerebellum, cortex cerebral, vase sanguine 1B 515 5 Ca2+, PKC 1D 560 20 Ca2+, PKC
splin, rinichi, rinichi aorta, aorta creier fetal cortex cerebral vase sang
Subtipuri de receptori 2-adrenergici 2A 2B 2C 461 4 cAMP inim,plmn aorta, hipocampus bulb olfactiv,
Aminoacizi 450 450 Cromosom 10 2 Cale efectoare cAMP cAMP Distribution pancreas, ficat, intestin subire, talamus locus ceruleus hipocampus
Subtipuri de receptori -adrenergici 1 Aminoacizi Cromosom Cale efectoare Distributie 477 10 cAMP 2 413 5 cAMP 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
Fenotip
Scderea presiunii arteriale Scderea presiunii arteriale i a rspunsului la stimulenii SNC Scderea presiunii arteriale Creterea activitii simpatice, tahicardie Scderea rspunsului vasoconstrictor la agonitii 2 Fr un fenotip f ti evident id t Majoritatea mor prenatal Modificri de tonus vascular i de metabolism energetic n stres Modificarea concentraiilor de leptin i insulin dup tratamentul cu agoniti
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
Sistemul Dopaminergic (Neurochemistry of Consciousness. Neurotransmitters in mind by Elaine Perry,Heather Ashton, Allan Young. John Benjamins BV. 2002)
sinapsa glutamatergic
Sinapsa glutamatergica
Transportori sinaptici
sinapsa GABAergic
Benzodiazepines Nonbenzodiazepine (Zolpidem) Barbiturice Methaqualone Baclofen Muscimol Progabide Tiagabine Bicuculline Metrazol Flumazenil
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
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
Neuron presinaptic
Neuron postsinaptic
Gk PLC
DAG
Ptdins(4,5)P2
[Ca2+]