How and why are calcium currents curtailed in the skeletal muscle voltage‐gated calcium channels?


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from wiki

"Cav1.1 also known as the calcium channel, voltage-dependent, L type, alpha 1S subunit, (CACNA1S), is a protein which in humans is encoded by the CACNA1S gene.[5] It is also known as CACNL1A3 and the dihydropyridine receptor (DHPR, so named due to the blocking action DHP has on it)"

Dihydropyridine class L-type calcium channel blockers include Nimodipine etc...

How and why are calcium currents curtailed in the skeletal muscle voltage‐gated calcium channels?

"As indicated by their name, voltage‐gated calcium channels (CaVs) are capable of sensing the depolarization of membrane potentials and in response to this electrical stimulus open a calcium‐selective channel pore. Accordingly, their primary role is in conducting activity‐regulated calcium influx in excitable cells. However, there is one notable exception: the skeletal muscle calcium channel CaV1.1.

This member of the CaV channel family has the same structure as all the other CaVs, with four voltage‐sensing domains (VSDs) grouped around a single ion pore, but its activation by skeletal muscle action potentials does not result in substantial calcium influx into muscle cells. Instead, its voltage‐dependent activation is directly transmitted to opening of the calcium release channel (type 1 ryanodine receptor; RyR1) in the sarcoplasmic reticulum (SR).

Therefore, in skeletal muscle CaV1.1 primarily functions as a voltage sensor for excitation–contraction (EC) coupling, but not as a calcium channel (Melzer et al. 1995).

Indeed, it has long been known that calcium influx through CaV1.1 is dispensable for EC coupling in skeletal muscles of most vertebrates (Armstrong et al. 1972), although during long‐lasting tetanic stimulation a small L‐type calcium current (LTCC) may contribute to refilling of the SR calcium stores and thus help to maintain muscle performance during prolonged activity (Robin & Allard, 2015).

Nonetheless, it appears paradoxical that skeletal muscle contraction – the prototypical calcium regulated cell function – involves a member of the CaV family with limited channel function."