Skeletal muscle CaV1.1 channelopathies.
CaV1.1 is specifically expressed in skeletal muscle where it functions as voltage sensor of skeletal muscle excitation-contraction (EC) coupling independently of its functions as L-type calcium channel. Consequently, all known CaV1.1-related diseases are muscle diseases and the molecular and cellular disease mechanisms relate to the dual functions of CaV1.1 in this tissue. To date, four types of muscle diseases are known that can be linked to mutations in the CACNA1S gene or to splicing defects. These are hypo- and normokalemic periodic paralysis, malignant hyperthermia susceptibility, CaV1.1-related myopathies, and myotonic dystrophy type 1. In addition, the CaV1.1 function in EC coupling is perturbed in Native American myopathy, arising from mutations in the CaV1.1-associated protein STAC3. Here, we first address general considerations concerning the possible roles of CaV1.1 in disease and then discuss the state of the art regarding the pathophysiology of the CaV1.1-related skeletal muscle diseases with an emphasis on molecular disease mechanisms.
['Flucher|Bernhard E|BE|0000-0002-5255-4705']
D048868:Adaptor Proteins, Signal Transducing D000818:Animals D020746:Calcium Channels, L-Type D053447:Channelopathies D006801:Humans D018482:Muscle, Skeletal D009154:Mutation
Skeletal muscle Malignant hyperthermia susceptibility Myotonic dystrophy Native American myopathy CaV1.1-myopathy Hypokalemic periodic paralysis Voltage-gated calcium channel