User Visitor Login
English only
EPFL > FSV > BBP > Channelpedia
Ion channels
Logged in as a Visitor.


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


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.


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


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


Accession Name Definition Evidence


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.



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


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])



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


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]).



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