Cavs

Question 1

Functionality of Cavs and which Cavs are there?

Answer 1

Functionally CaVs are closed at RMP (-50 - -80 mV) but activated by depolarization. Based on this and pharmacological properties the 10-cloned α-subunits can be grouped in three families:

CaV1 (L-type): high-voltage-activated dihydropyridine-sensitive calcium channels
* Require MP of -20 to +10 mV to activate

CaV2: high-voltage-activated dihydropyridine-insensitive channels

CaV3 (T-type): low-voltage-activated
* Currents which at much more negative membrane potentials, typically -50 to -40 mV

Question 2

How is the structure and molecular biology of Cavs?

Answer 2

The CaVs consist of a large α-subunit, a 24-TM unit – appr. 2000 amino acid residues.
The positive voltage-sensing domain is in the S4 segments, and the pore loops are at S5-S6 with the pore loops and S6 segments believed to line the channel lumen.

CaVs are 1000-fold selective for Ca2+ ions over Na+ and K+. The Selectivity is created by a ring of four negatively charged glutamic acid residues projecting into the ion channel pore – one residue by each of the four pore loops.

Subunits:
- CaVs consisting of only the α1 subunit forms a functional ion channel
- Native CaVs form multisubunit complexes with cytoplasmic β subunit, an extracellular membrane leaflet anchored α2δ subunit, and a 4-TM spanning γ subunit.
The role of the subunits is to regulate surface expression, gating, and pharmacological properties.