NEURO II

Neural Conduction and Synaptic Transmission

I. Resting Membrane Potential

® Membrane potential – the difference in electrical charge between the
inside and the outside of a cell (dintre citosol și lichidul extracelular)
® To record a neuron’s membrane potential, it is
necessary to position the tip of one electrode
inside the neuron and the tip of another electrode
outside the neuron in the extracellular fluid
® Resting potential – starea de repaus a neuronului,
care se inregistreaza la -70mV; indică faptul că
potențialul din interiorul neuronului aflat in repaus
este cu aproximativ 70 mV mai mic decât cel din
afara neuronului; se numeste stare polarizată
® Starea de repaus sau starea polarizata:
 mai multi ioni de Sodiu (Na+) in lichidul
extracelular
 mai multi ioni de Calciu (Ca-) in lichidul
extracelular
 mai multi ioni de Potasiu (K+) in citosol
 mai multe Proteine- (diversi ioni de
proteine incarcati negativ) in citosol

® Mai multe mecanisme au functia de a asigura

pastrarea potentialului de membrana la valoarea
de -70mV:
1. Mecanisme de omogenizare (distributie
egala):
 Gradientul de concentratie (1) –
ionii tind sa se miste din zone cu
concentratie mare in zone cu
concentratie mica
  Presiunea electrostatica (2) – ionii pozitivi sunt atrasi
inspre membrana deoarece citosolul este mai incarcat
negativ decat lichidul extracelular

2. Mecanisme de distributie inegala:

 Conductanta selectiva a membranei
 Pompa de sodiu-potasiu (3) (consuma 70% din ATP-ul din
celula) – scoate 3 ioni de Na+ si introduce 2 ioni de K+ in
citosol

II. Generation, Conduction and Integration of Postsynaptic Potentials

® neuronii senzitivi sunt stimulati de un eveniment din mediul extern (stimul)
® interneuronii sunt stimulati de neurotransmitatori
® Atunci când neuronii sunt declanșati, eliberează din butonii terminali
substanțe chimice numite neurotransmițători, care se difuzează prin
fisurile sinaptice și interacționează cu molecule de receptori specializati de
pe membranele receptive ale următorilor neuroni din circuit. Atunci când
moleculele de neurotransmițători se leagă de receptorii postsinaptici,
acestea au de obicei unul dintre cele două efecte, în funcție de
neurotransmițător, receptor și neuronul postsinaptic în cauză
® Neurotransmitatorii determina potentiale postsinaptice locale, care pot fi:
 excitatorii (care produc depolarizarea membranei) more likely
that neuron will fire
 inhibitorii (care produc hiperpolarizarea membranei) less likely
that neuron will fire
® PPSE și PPSI sunt proporționale cu intensitatea semnalelor care le
determină: semnalele slabe generează potențiale postsinaptice mici, iar
semnalele puternice produc cele mari
® Potentialele post-sinaptice se pot suma (spatial sau temporal) si astfel se
atinge pragul de depolarizare, declansandu-se potentialul de actiune
® Action potential is a massive but momentary, lasting for 1 millisecond,
reversal of the membrane potential from about -70mV to about +50 mV
® Neurons integrate/sum incoming signals in two ways: over space and time
 Membrane potential

® Spatial summation Action potential

® Temporal summation
® Each neuron continuously integrates signals over both time and space as it
is continually bombarded with stimuli through the thousands of synapses
covering its dendrites and cell body
gradually

III. Conduction of Action Potentials

® Potentialul de actiune se declanseaza doar daca sumarea PPS atinge pragul
de depolarizare (+50mV);
® Action potential include:

A. DEPOLARIZAREA
 este activat pragul de excitare al tesutului nervos de catre PPSE
 se inregistreaza +50mV
 se deschid canalele de Sodiu (Na+)
 fortele se sumeaza si actioneaza simultan asupra membranei din
exterior in interior (presiune de 120mV) conducand foarte multi
ioni de Sodiu (Na+) in interiorul celulei
 se produce influx de sodiu
 Spike potential/overshoot – maximul depolarizarii.
  treptat, se deschid si canalele de potasiu si se produce un eflux de
potasiu
 la potasiu, fortele actioneaza in directie opusa, din interior spre
exterior, cu o presiune de 20mV, conducand ionii de potasiu in
exteriorul celulei
 dupa aproape 1 milisecunda, se inchid canalele de sodiu, proces
care marcheaza incheierea fazei de crestere

B. REPOLARIZAREA
 in acest moment, are loc procesul de inchidere al canalelor de
potasiu (lent si gradual)
 intra in actiune pompa de sodiu-potasiu care scoate (-) trei ioni de
sodiu si introduce (+) doi ioni de potasiu – forta care actioneaza in
directia restabilirii starii de repaus.
*inca ies ioni de potasiu, dar canalele de potasiu sunt in procesul de
inchidere

C. HIPERPOLARIZAREA
 in acest moment, canalele de potasiu sunt inchise
 Pompa de sodiu-potasiu contribuie la restabilirea starii de repaus
 valoarea minima – posthiperpolarizare

® Refractory period – is responsible for two important characteristics of

neural activity:
 it is responsible for the fact that action potentials normally travel
along axons in only one direction
 it is responsible for the fact that the rate of neural firing is related to
the intensity of the stimulation
® Absolute refractory period –a brief period of about 1 to 2 milliseconds
after the initiation of an action potential during which it is impossible to
elicit a second one
® Relative refractory period – the period during which it is possible to fire
the neuron again but only by applying higher-than-normal levels of
stimulation

® Axonal Conduction of Action Potentials

® once an action potential has been
generated, it travels passively
along the axonal membrane to
the adjacent voltage-activated
sodium channels, which have yet
to open; the arrival of the
electrical signal opens these
channels, thereby allow Na+ ions
to rush into the neuron and
generate a full blown action
potential on this portion of the
membrane; this signal is then
conducted passively to the next
sodium channels, where another
action potential is actively
triggered; these events are
repeated again and again until a
full-blown action potential is
triggered in all the terminal buttons
® the wave of excitation triggered by the generation of an action potential
near the axon hillock always spreads passively back through the cell body
and dendrites of the neuron
® Antidromic conduction – if electrical stimulation of sufficient intensity is
applied to the terminal end of an axon, an action potential will be generated
and will travel along the axon back to the cell body
® Orthodromic conduction – axonal conduction in the natural direction,
from cell body to terminal buttons
 ® Conducerea pasiva – semnalul electric slabeste pe masura ce este condus,
din cauza faptului ca depinde de distributia ionilor din interiorul si
exteriorul membranei; PPS sunt conduse pasiv, doar pe o portiune foarte
mica, pentru ca au un semnal scazut (cativa mV) si pentru ca dispar foarte
repede, din cauza decrementului; sunt locale si nepropagabile
® Conducerea activa – semnalul este mentinut datorita canalelor ionice care
se dechid; PA este condus pasiv de-alungul membranei pana intalneste un
canal de sodiu, care se deschide si permite ionilor de sodiu sa intre in
interiorul membranei, astfel, semnalul PA este reintensificat/resetat;
procesul se repeta pana la butonii terminali; este propagabil si nu se pierde
® Conducerea continua – are loc in axonii nemielinizati, fara decrement,
insa foarte lent (cca. 1m/s)
® Conducerea saltatorie – are loc in axonii mielinizati, rapid datorita tecii de
mielina si fara decrement datorita
nodurilor Ranvier; la nivelul
nodurilor Ranvier, PA este
reintensificat datorita canalelor
ionice care permit intrarea ionilor de
sodiu in interiorul celulei, resetand
semnalul electric; PA nu are loc
niciodata singur; frecventa PA
codifica informatia (cca. 10-60m/s)

IV. Synaptic Transmission: Chemical Transmission of Signals among Neurons

SINAPSA

® Tipuri de sinapsa:
 axo-dendritice
 axo-somatice
 axo-axonice
 dendro-dendritice
  sinapse chimice (care elimina o
substanta chimica inervatoare)
 sinapse electrice (elimina semnale
electrice)

® Structura sinapsei:
 Terminal presinaptic – zona
activa, o portiune din membrana
cu o densitate mare de pori prin
care sunt eliberati
neurotransmitatori
 Componenta postsinaptica –
densitatea postsinaptica, zona cu o
densitate mare de proteine
receptori postsinaptici, care se
modifica frecvent, in functie de
neurotransmitatori
 ionotropici – au un canal
ionic in structura lor;
receptarea unui
neurotransmitator (cuplare
ligand) determina
deschiderea canalului ionic conducand la un potential
postsinaptic
 metabotropici – nu au canale ionice in structura lor, insa au
o proteina de semnalizare, care, in momentul cuplarii cu un
neurotransmitator, elibereaza o subunitate: Proteina G;
aceasta dupa ce a fost eliberata poate determina un PPS,
legandu-se de un canal ionic sau poate stimula sinteza unui
mesager de ordinul II

*un neurotransmitator este ligand pentru receptorul sau.

 *comunicarea intre celule se numeste semnalizare celulara.

® Semnalizarea sinaptica – un tip de semnalizare celulara a SN

 semnalul electric din terminalul presinaptic declanseaza un semnal
electric in densitatea postsinaptica – semnalul electric se transmite
continuu de pe un neuron pe altul, pentru ca sunt destul de apropiati
 semnalul electric declanseaza un semnal chimic si abia apoi un
semnal electric – cantitatea de neurotransmitatori este proportionala
cu frecventa PA

® Sinteza, Stocarea si Transportul Neurotransmitatorilor

 Sinteza neurotransmitatorilor se realizeaza in corpul
neuronului/citoplasma
 Stocarea se realizeaza prin impachetarea in vezicule spinaptice
langa membrana presinaptica (exista exceptii: neurotransmitatorii
molecule mici sunt sintetizati si impachetati in citoplasma butonului
terminal)
 Transportul se realizeaza axoplasmatic, anterograd

® Exocitoza Neurotransmitatorilor
 procesul de eliberare a neurotransmitatorilor
 la nivelul zonei active/presinaptice, exista canale voltaj-dependente
de Ca2+ care, in repaus, sunt inchise.
 atunci cand sunt stimulate de PA, se deschid si are loc un influx de
ioni Ca2+
 astfel veziculele cu NT se mobilizeaza si merg spre zona activa,
declansand exocitoza neurotransmitatorilor in fanta sinaptica

® Detectarea Neurotransmitatorilor de catre Receptori

 neurotransmitatorii se cupleaza pe receptorii postsinaptici si se
initiaza potentiale postsinaptice
 direct – prin receptorii ionotropici (ligand-activated ion channels)
  indirect – prin intermediul altor proteine care interactioneaza cu
receptorii metabotropici (signal proteins and G proteins)

® Degradarea sau Recaptarea Neurotransmitatorilor

 Degradarea se realizeaza prin inactivarea chimica de catre enzime a
NT in fanta sinaptica sau prin captarea la nivel de astrocita
 Recaptarea se realizeaza cu ajutorul unor proteine numite
transportori, care conduc NT inapoi in terminalul presinaptic

V. Neurotransmitters
® Classes
® Small-molecule neurotransmitters
 amino acids
 monoamines
 acetylcholine
 unconventional neurotransmitters (their mechanisms of action are
unusual)
® Large-molecule neurotransmitters
 neuropeptides
® most neurotransmitters produce either excitation or inhibition, not both, but
a few produce excitation under some circumstances and inhibition under
others

® The Roles and Functions

 AMINO ACID NEUROTRANSMITTERS
 The neuro transmitters in the vast majority of fast-acting,
directed synapses in the central nervous system are amino
acids – the molecular building blocks of proteins. The four
most widely studied amino acid neurotransmitters are
 GLUTAMATE
 ASPARTATE
 GLYCERINE
 GAMMA-AMINOBUTYRIC ACID (GABA)
 The first three are common in the proteins we consume,
whereas GABA is synthesized by a simple modification of
the structure of glutamate. Glutamate is the most prevalent
excitatory neurotransmitter in the mammalian central
nervous system. GABA is the most prevalent inhibitory
neurotransmitter

 MONOAMINE NEUROTRANSMITTERS
 Monoamines are another class of small-molecule
neurotransmitters Each is synthesized from a single amino
acid—hence
 The name monoamine (one amine). Monoamine
neurotransmitters are slightly larger than amino acid
neurotransmitters, and their effects tend to be more diffuse
 There are four monoamine neurotransmitters
 DOPAMINE
 EPINEPHRINE
 NOREPINEPHRINE
  SEROTONIN
 They are subdivided into two groups, catecholamines and
indolamines, on the basis of their structures. Dopamine,
norepinephrine, and epinephrine are catecholamines. Each is
synthesized from the amino acid tyrosine. Tyrosine is
converted to l-dopa, which in turn is converted to dopamine
 Neurons that release norepinephrine are called
noradrenergic; those that release epinephrine are called
adrenergic.

 ACETYLCHOLINE
 Acetylcholine (abbreviated Ach) is a small-molecule
neurotransmitter that is in one major respect like a professor
who is late for a lecture
 Acetylcholine is the neurotransmitter at neuro-muscular
junctions, at many of the synapses in the autonomic nervous
system, and at synapses in several parts of the central
nervous system

 UNCONVENTIONAL NEUROTRANSMITTERS
 One class of unconventional neurotransmitters,
 (1) soluble-gas neurotransmitters, includes:
 NITRIC OXIDE and CARBON MONOXIDE
 These neurotransmitters are produced in the neural
cytoplasm and immediately diffuse through the cell
membrane into the extracellular fluid and then into nearby
cells. They easily pass through cell membranes because they
are soluble in lipids. Once inside another cell, they stimulate
the production of a second messenger and in a few seconds
are deactivated by being converted to other molecules. They
are difficult to study because they exist for only a few
seconds
 Another class of unconventional neurotransmitters is the
 (2) endocannabinoids, includes:
  ANANDAMIDE
 Like the soluble gases, the endocannabinoids are produced
immediately before they are released. Endocannabinoids are
synthesized from fatty compounds in the cell membrane;
they tend to be released from the dendrites and cell body;
and they tend to have most of their effects on presynaptic
neurons, inhibiting subsequent synaptic transmission

 NEUROPEPTIDES
 About 100 neuropeptides have been identified. The actions
of each neuropeptide depend on its amino acid sequence.
 One category (pituitary peptides) contains neuropeptides
that were first identified as hormones released by the
pituitary, a
 Second category (hypothalamic peptides) contains
neuropeptides that were first identified as hormones released
by the hypothalamus
 Third category (brain–gut peptides) contains neuropeptides
that were first discovered in the gut.
 Fourth category (opioid peptides) contains neuropeptides
that are similar in structure to the active ingredients of
opium, and the fifth (miscellaneous peptides) is a catch-all
category that contains all of the neuropeptide transmitters
that do not fit into one of the other four categories

VI. Pharmacology of Synaptic Transmission and Behavior

® Drug Influence on Synaptic Transmission
 Drugs that facilitate the effects of a particular neurotransmitter are
said to be agonists of that neurotransmitter
 Drugs that inhibit the effects of a particular neurotransmitter are
said to be its antagonists
® Behavioral Pharmacology