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Cav1.1

calcium channel, voltage-dependent, L type, alpha 1S subunit
Synonyms: cacna1s cav1.1 ca1.1 MHS5 HOKPP hypoPP CCHL1A3 CACNL1A3. Symbol: Cacna1s

Introductions


The voltage-gated Ca2+ channel CaV1.1 functions as a voltage sensor in skeletal muscle excitation-contraction (EC) coupling. (Tuluc [1227])

CACNA1 (also known as MHS5; HOKPP; TTPP1; Cav1.1; HOKPP1; hypoPP; CCHL1A3; CACNL1A3) encodes Cav1.1, one of the five subunits of the slowly inactivating L-type voltage-dependent calcium channel in skeletal muscle cells. Mutations in this gene have been associated with hypokalemic periodic paralysis, thyrotoxic periodic paralysis and malignant hyperthermia susceptibility.

http://www.ncbi.nlm.nih.gov/gene/779

Genes


Only one CaV1.1 splice variant has so far been described in rabbit skeletal muscle (Perez-Reyes [1235]). Skipping of exon 29 shortens the extra-cellular loop connecting transmembrane domains IVS3 and IVS4. This loop is a conserved splicing site of CaV1 a1 subunits that has been shown to generate differentially distributed and functionally distinct channel variants. (Tuluc [1227]

Cacna1s : calcium channel, voltage-dependent, L type, alpha 1S subunit

RGD ID Chromosome Position Species
70983 - Rat
733918 1 137949478-138016399 Mouse
736857 1 201008640-201081694 Human

Transcripts


Acc No Sequence Length Source
NM_053873 NCBI
NM_001081023 NCBI
NM_014193 NCBI
NM_000069 NCBI

Ontologies


Accession Name Definition Evidence

Interactions


I-II loop of Ca(v)1.1 was identified as the domain interacting with caveolin-3, with an apparent affinity of 60nM. Couchoux et al [1228] showed a direct molecular interaction between caveolin-3 and the dihydropyridine receptor which is likely to underlie their functional link and whose loss might therefore be involved in pathophysiological mechanisms associated to muscle caveolinopathies.

Proteins


Structures


See figure 1 in Striessnig et al [1230] for a detailed structure drawing of Cav1.1.

Distributions


Cav1.1 in muscle cells is located in triad junctions in close apposition to the Ca2+ release channel (type 1 ryanodine receptor (RyR1)) in the sarcoplasmic reticulum (SR). (Tuluc [1227])

Expressions


Functionals


Cav1.1 and Cav1.2 subunits may substitute for Cav1.3 to maintain bone response to mechanical loading. (Zhao[1229])

Kinetics


On depolarization of the surface membrane, CaV1.1 undergoes a conformational change that rapidly activates the Ca2+ release channel, presumably via protein-protein interactions. Ca2+ influx through the voltage-gated Ca2+ channel is not required for activation of skeletal muscle EC coupling. L-type Ca2+ currents through CaV1.1 activate very slowly and at more positive membrane potentials than EC coupling (for review, see Melzer et al. [1234]). Therefore, it is unlikely that during a short skeletal muscle action potential Ca2+ channels contribute significant amounts of Ca2+ to the transients that trigger contraction. (Tuluc [1227])

Cav1.1 channels (which also contain a γ-subunit) carry very slowly activating Ca2+ inward currents, too slow for providing Ca2+ to the contractile machinery in response to millisecond depolarizations eliciting muscle contraction. Although the fast conformational changes of their voltage-sensing domains induce pore opening very slowly, they are quickly transmitted to the sarcoplasmic reticulum (SR) ryanodine receptors (RyR1), thus serving as fast voltage sensors for SR Ca2+ release. This seems to be accomplished through a close physical association of Cav1.1 channels in the T- tubular membrane and RyR1 in the junctional SR of the skeletal muscle triads (Kugler [1236]).

Models


References


[1227 : 19134469]
[1228 : 21262376]
[1229 : 20516636]
[1230 : 20213496]
[1231 : 18718913]
[1232 : 17906876]
[1233 : 17899167]
[1234 : 7742348]
[1235 : 2173707]
[1236 : 14627713]

Credits