Flashcards in misc Deck (5)
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1
Effect of the beta subunit on the alpha in VGICs
Alpha subunits can function on their own; the accessory or beta subunits are more diverse and modulate the function of the alpha.
- can regulate expression levels, location and trafficking
- can alter voltage dependence of activation or inactivation
- can bind drugs that modulate function
- phosphorylation of beta su can regulate VGIC functions
2
Molecular Properties of VGICs
- Aqueous pore that controls selectivity for Na+/K+/Ca2+ ions
- All VGICs have similar pore structure
- K+ channels are 100-1000 fold selective over K+
- Na+ channels are 10fold selective for Na+ over K+
- Ca2+ channels are 1000 fold selective for Ca2+ over other cations
3
Opening and closing of VGICs
- VGIC open in response to changes in membrane potential
- VGICs contain a voltage sensor, which moves in response to changes in membrane potential
- Regulatory domains in some related channels can regulate opening of channels - e.g. Ca2+ activated K+ channels, cAMP regulated K+ channels
- Deactivation: when the membrane potential reverses back to its resting state the channel may close (opposite of activation)
- Inactivation: voltage dependent Na+ channels will close immediately after being activated (even when there is still depolarisation). Ball and chain model for inactivation - influx of +ve charge will cause an intracellular domain to swing into the open pore of the channel to prevent ion flow.
4
Regulation of VGICs
- Phosphorylation of VGICs can alter the channel properties such that it responds in a different manner to allow the cell to respond to different physiological stimuli - allows for rapid changes in channel function (seconds or less)
- e.g. PKC causes phosphorylation of a single residue in the alpha su of a Na_v, to slow the rate of channel inactivation
- e.g. PKA phosphorylation slows the rate of Ca_v channel activation and shifts the voltage dependence so that it is activated at more negative potentials
5
