ion channels n ionotropic receptors Flashcards
why is phosolipid bilyer called as parallel capacitor and resistor
ions are unable to penetrate the lipid bilayer of the cell membrane(resistor)
and phospholipid bilayer (insulator ) separates the intracellular space from the extracellular space
the intrinsic electivcal conducted of this structure is very poor(resistor function)
presence of ion channel effect on resistance
since the ion channel act as conduits, allow fro flow of ions across the phospholipid bilayer
- decreased resistance
what is membrant potential
generated by the differential distribution of ions, particularly Na+, K+ and Cl-
unequal distribution is maintained by ionic pumpus and exchanges
usually -60–75 (diff resting potential for. iff cells )
can also change while the cells are at different level of activity
what are important ions in resting potential and where are they present at higher conc
na -outisde
k-inside
ca-outside
cl-outside
what are the propertioes of ion channel
rate and direction of ion movemnr thru the pores is governed by electrochemical gradient of the ions in question, which is a function of its concentrations on either side of the membrane , and of the membrane potential
- selectivity( selective to specific ions)
- gating properties (type of control of the ion channel)
ion channels protein
transmembrane protein
- pore domain
have voltage sensing domain
ligand binding domain
span across the membrane
what are the different type of gatinf of the ion channels
passice (kk + leak channel)
voltage gated (Na, ca, k voltage gated channel)
mechnically gated(baroreceptors and hair cells)
ligand gated (nicotinic acetylcholine, GABA receptor )
what s action potential mechanism
- resting potenital (with ligand gat are closed )
- stimulus cause some channel to open
- when the threshold is reached, the action potential occue, more gated channel opens
- depolarization occcuer: sodium rush into the cell
- when the voltage is more than 30mv, voltage channel NA+ closes
- k+ channel opens
- repolarisation occur where k rush out of the cell
- voltage will decrease below -70
- k + channel clsoes
- an + and k+ pump restore the resting potential of the cell
how does signalling happen in one direction only?
when is it depolarsing the behind is repolarising, allowing for signal to only move in one direction
two different type of refracotry period an what they do
absoulte and relative
absolute means that another action potential cannot be triggered during this time
Na+ channel are briefly inactviated
and membrane need to be hyper polarised before depolarisation can happen
for relative refractory period,
a stong stimular can cause Ap
- Since membrane is below the resting potential, strong EPSP can trigger the threshold
what improves the AP propogation
myeline shealths which are rich in lipids, they are made of oligodendrocytes in CNS and svuann cell in PNS
what happens when AP reaches the end
depolarisaion trigger voltage gaterd channel
ca2+ channel open
ca2+ enetr
exocytosis of vesicles
neurotransmitters released into synaptic cleft
neurotransmitters bind to receptor on post synaptic neurons
EPSP/IPSP
Trigger another AP
what happens when sodium channel is clocked
increase in threshold for excitation
slow impulse conduction
decreased rate of rise of AP
decreased amplitude of AP
when blocked at critical length, propagation across the blcojed area is impossibl
what are drugs used as sodium blocker
local anaestheitc agents , cocaine, lidocaine
what are channels that regulate the calcium in and out
ligand gated ca channle
voltage gated ca channel
ryanodine receptor
store operated calcium channels
NA ca exchange
state the calcuim effect on cardiac/skeletal msucle
AP travel down the sacolemma
causes openong of the ryanodine and voltage gated ca channel
ca rush into the cell
ca diffuse with cytoplasm towards active filaments(g actin monomers)
ca bind to troponin
confirmation change in troponin
tropomyosin move
g actin active site is exposed, myosin bind to g actin
form cross bridge that causes muscular contraction
state the calcium effect on smooth muscles
when there is a increase in free intracellular calcium
increase in calcium influx into the cell
or by release of calcukm from internal stores
free calcium bind to the calmodulin
calcium calmodulin activates myosin light chain kinase
this phosphorylates the myosin light chains in the presence of ATP
myosin light chains are found on the myosin heads
myosin light chains phsophorylation leads to smooth muscle contraction
what is the effect of the L type calcium blockade in the heart
reduced in contractility
decreases sinus node pacemaker rate
decrease atrioventricular node condition velocity
use In the treatment of angina and supraventricular tachyarrhythamias
what is the effect of the L type calcium blockade in the smooth muscles
losg lasting relaxation
dilate peripheral arterioles and reduce blood pressure
use in the treatment of hypertension
list other ligand gated channels
glutamate
acetylcholine
GAB
5HT
ATP
List the calcium channel blockers
amiodpine
verapamil
what are the molecules for GABA receptor
benzoidiazepines and zolpidem
what do GABA regualte
it is a gab RECEPTOR CHOLORIDE CHANNEL COMPLEX
what does GABA do ?
postsynaptic
increse the cl- influx from outside
what are the selective agnoist and antagosit of GABA
agonist : isoguvacine and antagonist :biuculline
what are the regulatory sites on the GABA
benzodiazepine and barbiturate sites
what do benzodiazepines do ?
potentiate GABA action by increasing the frequency of GABA induced channel opening
what does phenobarbital do?
increases the frequence and duration of opening
what are the clincial application of benzodiazepines
anti anxity agenst
sedative agents
anti-epileptic drugs
general anaesthetic agents
what are nicotinic acetylcholine receptors
extensive projection out of the membrane
chaneel pore with a narrow spot
closed intracellular end of the channel with laterally places outlets for ions
- subtype found in the skeletal muscles, neurons and autonomic ganglia
what are the seletive agonist and antagonist of nicotinic acetylcholine receptors
nicotine is the agonist
a bengartoxin is the antagonist
what do neuromuscular blocking drugs
block nitonic receptors function resulting in skeletal muscle paralysis
- used during surgical procedures as muscles relaxants
how are neuromuschlar blocking drugs divided?
non depolarising drugs - act as antagonist at the nicotinic receptors
depolarising drugs- act as agnosit at the nicotinic receptors : causing persisten depolarising following by desensitization of the nictonic receptors
what are non depolarizing neuromuscular blocking drugs
pancuronium, atracurium and tubocurarine
what are depolarizing neuromuscular blocking drugs
succinylcholine
name 2 dieases due to defective ino channel functions
function 1: cystic fibrosis
function 2: long qt syndrome
what is cyctsic fibrosis
mutation in the epithelial chloride channel cftr(transmembrane conductance regulator)
- deletion of the phenylalanine at position 508, the defective protein cannot reach the surface membrane
- causes impaired cl, conductance in the membrane of the secretory epithelial cells
— in the lungs, this loss of CFTR activity leads to the dehydration in the airway epithelia, thickening mucus, build up of thick mucus promotes bacterial growth and potentially serious lunch infection
what is long qt syndrome
mutation in the cardiac potassium channels(HERG, KCNQ1, KCNE1, KCNE2)
loss of function and reduced potassium currents
long AT intervals in the electrocardiogram, reflecting the delayed repolarization of the caridia action potential
– results in irregular heart beat — and muscle weakness
