Lecture Notes

Part 3 molecular and functional characterisation of voltage-gated calcium
channels

Excitation-secretion coupling




Functional classification of voltage-activated calcium currents

 L-type = high-voltage activation (HVA)
- Long-lasting
- Blocked by dihydropyridines
- Involved in muscle contraction
 N-, P/Q-,R-type = high-voltage activation (HVA)
- Involved in neurotransmitter release
- Not blocked by dihdropyridines
 T-type = low-voltage activation (LVA)
- Transient
- Not blocked by dihydropyridines

Purification of voltage-gated calcium channel

 An L-type calcium channel protein was purified from rabbit skeletal muscle (T-tubule membranes) using radiolabelled
nitrendipine (a dihydropyrifdine) to monitor its purification
- Similar to chromatography but slightly different
 A ~ 170 kDa protein was purified and a cDNA encoding this protein was sequenced (1873 AA)
 Analysis of the sequence revealed striking similarity with voltage-gated sodium channels
 L-type Ca channel was the first Ca channel to be purified.



The voltage-gated channel superfamily

 A different class of channel belong to the same family of protein of voltage-gated ion channels