Lecture 3 Flashcards
3 main types of ion channel
Voltage gated ion channel
Neurotransmitter ion channel
Secondary messenger ion channel
Voltage gated ion channels
- Na+ ion channels open, allowing for Na+ influx, more positive membrane voltage
- K+ ion channels open, efflux causes more negative membrane voltage
- Ca2+ ion channels open, allowing for influx, increases cytosolic calcium ion levels
Neurotransmitter gated channels
Gating of these channels is via extracellular substances
Examples of neurotransmitters which open NGC
acetyl choline and glutamate both select for cations in action potentials
GABA and glycine both select for Cl- ehich inhibits APs
Second messenger-gated channels
Gating of channels is via a cytosolic second messenger.
Example of Second messenger-gated channels
Cyclic nucleotide-gated channels (CNGCs)
Cation selective and gated by cAMP or cGMP
Retinal vs olfactory
Retinal: Light into action potentials
Olfactory: Chemicals (smells) into action potentials
Second messenger-gated channels
Inositol 1, 4, 5 triphosphate (IP3) receptors:
These are Ca2+-selective and release Ca2+ from the ER to elevate cytosolic Ca2+ during cell signalling events.
Structure of voltage gated ion channels
6 TMS domains (S1-S6)
Pore domain
Voltage senser composed of many positively charged a.a. residues
Long ‘N’ terminus forms ‘ball and chain’ arrangement involved in inactivation
What forms selectivity filter and pore region?
P-loop
Conserved amino acids in P-domain
K+ channels - GYG - Glycine, tyrosine, glycine
Ca2+ channels - E - glutamate
Na+ channels - DEKA - aspartate, glutamate, lysine, alanine
Where is voltage sensing achieved and with what sequence?
S4
XXRXXRXXRXXRXXRXXK
Sliding helix model:
Change in voltage forces the arginine residues to move up through the membrane which in turn forces a conformational change which opens the gate
Inactivation of voltage-gated channels: the ball and chain model
K+ channel with N-terminus amino acid residues removed (mutant) - Constant activity
Mutated K+ channel with N terminus polypeptide added back - Slower decrease in ion channel activity
K+ channel inactivation (wild-type)