Voltage gated channels Flashcards
What are the major classes of vgc
K, Na, Ca
distinguished by ion selectivity
describe the basic features of K channels
diverse
open slowly at depol (vgc)
leak K channels active at rest
restore + maintain resting state
describe the basic features of Na channels
open rapidly at depolarisation
pos feedback loops
inactivation limits their duration
provide excitatory response
describe the basic features of Ca channels and the cellular functions of ca
provide transient increase in intracellular ca
ca reulates neurotransmitter release, muscle contractions, secretion of hormones, neuronal outgrowth, regulations of channels and enzymes
ca is removed by transporters and binding and is an important second messenger
what drives the transition between open and closed states
membrane potential
a positive membrane potential drives towards open state
a negative membrane potential drives towards closed state
what governs the likelihood of an ion channel being open/closed
probability
the longer a channel is open, the longer it will remain closed
describe tetramer structure
one tetramer has 4 subunits
each subunit has 6 transmembrane domains
the 4th transmembrane domain has the voltage sensor
some subunits have special sensors and are also sensitive to things like calcium concentration
Why do Na and Ca channels appear different in structure
They have 4 pseudosubunits
eg Na ahs 2 subunits built into one amino acid sequence
these are linked together by cytoplasmic loops and are encoded for by a single chain, unlike other subunits which are individually encoded for
what was the deal with hodgkin and huxley
by observing a channel at depolarisation they were able to determine that it had a multi step activation process, and basically discovered that all 4 subunits must be permissively configurated before the pore can open
this was centred around the probability of a pore opening …. x4
Why are s4 domains’ sequence important
highly conserved amino acid sequence indicates importance
bc of voltage detection ability
Describe how Na channels were cloned + significance
1st to be cloned, protein isolated by tetrodotoxin; a high affinity binding blocker. anf fit into the s4 vgc superfam
Which channels are included in the vgc superfam
K, inward rectifier K, TRP, Na. Ca, 2 pore leak
describe cloning from mRNA
retroviruses use RNa as genetic material
and synthesise DNA by using reverse transcriptase
What are the major classes of Ca channels
High voltage activation (HVA) - require large depolarisation to open and have plateau responses ie don’t respond to inactivation
low volatge activation (LVA) - open below threshold and are transient responses so DO respond to inactivity