Voltage Gated Ion Channels Flashcards
what are voltage-dependent ion channels?
membrane proteins that conduct ions at high rates
regulated by voltage across membrane
what do voltage dependent ion channels play a fundamental role in?
generation + propagation of nerve impulse in cell homeostasis
what is the voltage sensor?
region of protein bearing charged AA
relocate upon chains in membrane electric field
what does the movement of the sensor initiate?
conformational change in gate of conducting pathway
thus controlling flow of ions
voltage gated Na+ channels
have 2 voltage sensitive gates
- at resting Em, one gate closed + other open
- when membrane depolarised, second gate opens
- after short time, second gate shuts
how may drugs affect the na+ channels in nerves?
- involved with AP
- local anaesthetics - lidocaine
- block channel + reduce pain
how may drugs affect the na+ channels in the heart?
- involved in generation of cardiac AP
- drugs can block na+ channels in arrhythmias
what does tetrodotoxin (TTX) block?
AP by binding to na+ channels
where is TTX found?
in puffer fish, toads, newts, blue ringed octopus
what does TTX poisoning cause?
paralysis of voluntary muscles (diaphragm)
breathing stops
loss of vagal regulation of heart rate + loss of sensation
numbness of lips + tongue
voltage gated k+ channels
only have one gate
gate activated by depolarisation
gate responds slower
what is the function of the k+ channels?
membrane depolarisation
inhibition of k+ flux —> long QT syndrome
black mamba snake venom + VGCs
- k+ channel blocker
- prevents repolarisation of nerve + muscle cells
- inc release of neurotransmitters
- prevents relaxation of muscle cells
describe the structure of voltage gated calcium channels (VGCC)?
- have diff subunits: alpha1, alpha2-delta, beta1-4, gamma
- alpha1 forms ion conducting pore
- subunits = target of drugs
what do voltage gated calcium channels include?
- neural N type channel blocked by w-conotoxin
- R type channel involved in poorly defined processes in brain
- closely related P/Q type channel blocked by w-agatoxins
- dihydropyridine-sensitive L-type channels responsible for excitation-contraction coupling of skeletal, smooth + cardiac muscle
- & for hormone secretion in endocrine cells
L-type ca2+ channels + smooth muscle contraction
- smooth muscle cell depolarised
- L-type calcium channels open
- influx of extracellular ca2+
- calmodulin binds
- activated calmodulin activates myosin light chain kinase
- phosphorylates myosin
- myosin forms cross bridges with actin
- smooth muscle fibre contracts
how may depolarisation be brought about?
- stretching of cell
- agonist binding G protein coupled receptor
- autonomic nervous system stimulation
what are DHPs used as?
calcium channel blockers
vasodilators in treatment od hypertension
what are verapamil and diltiazem used in?
calcium channel blockers
treatment of angina + arrhythmias
can depress cardiac function
