VOLTAGE-SENSITIVE CALCIUM CHANNELS (VSCC) MEDIATE THE
ENTRY OF CALCIUM IONS INTO EXCITABLE CELLS AND ARE ALSO INVOLVED IN
A VARIETY OF CALCIUM-DEPENDENT PROCESSES, INCLUDING MUSCLE
CONTRACTION, HORMONE OR NEUROTRANSMITTER RELEASE, GENE EXPRESSION,
CELL MOTILITY, CELL DIVISION AND CELL DEATH. THE ISOFORM ALPHA-1C
GIVES RISE TO L-TYPE CALCIUM CURRENTS. LONG-LASTING (L-TYPE)
CALCIUM CHANNELS BELONG TO THE 'HIGH-VOLTAGE ACTIVATED' (HVA)
GROUP. THEY ARE BLOCKED BY DIHYDROPYRIDINES (DHP),
PHENYLALKYLAMINES, BENZOTHIAZEPINES, AND BY OMEGA-AGATOXIN-IIIA
(OMEGA-AGA-IIIA). THEY ARE HOWEVER INSENSITIVE TO
OMEGA-CONOTOXIN-GVIA (OMEGA-CTX-GVIA) AND OMEGA-AGATOXIN-IVA
(OMEGA-AGA-IVA). CALCIUM CHANNELS CONTAINING THE ALPHA-1C SUBUNIT
PLAY AN IMPORTANT ROLE IN EXCITATION-CONTRACTION COUPLING IN THE
HEART.
VOLTAGE-DEPENDENT CALCIUM CHANNELS ARE MULTISUBUNIT
COMPLEXES, CONSISTING OF ALPHA-1, ALPHA-2, BETA AND DELTA SUBUNITS
IN A 1:1:1:1 RATIO. THE CHANNEL ACTIVITY IS DIRECTED BY THE
PORE-FORMING AND VOLTAGE-SENSITIVE ALPHA-1 SUBUNIT. IN MANY CASES,
THIS SUBUNIT IS SUFFICIENT TO GENERATE VOLTAGE-SENSITIVE CALCIUM
CHANNEL ACTIVITY. THE AUXILIARY SUBUNITS BETA AND ALPHA-2/DELTA
LINKED BY A DISULFIDE BRIDGE REGULATE THE CHANNEL ACTIVITY.
NCBI Summary:
Alpha 1C subunit of the voltage-dependent calcium channel; channel is of the L type and is expressed in the heart
General function
Channel/transport protein
Comment
Cellular localization
Plasma membrane
Comment
Ovarian function
Comment
Perez-Reyes E, reported the molecular diversity of L-type calcium channels. Evidence for alternative splicing of the transcripts of three non-allelic genes.
The diversity of L-type calcium channels was probed using the polymerase chain reaction and primers based on regions conserved in the L-type skeletal muscle (CaCh 1) and cardiac calcium channels (CaCh 2). Related sequences were amplified from human heart, hamster heart, rabbit heart, mouse ovary, mouse BC3H1 cells, and hamster insulin-secreting (HIT) cells. Sequencing of various clones revealed the presence of alternate splicing in gene products coding for CaCh 1, CaCh 2, and a related calcium channel. This related gene product, which we refer to as neuroendocrine or CaCh 3, is expressed in brain and endocrine cells. The diverse products can be explained by the use of alternate exons of equal size, which account for changes in amino acid composition, in combination with an alternate splice acceptor site or an exon skipping event, which produces channels of variable length. Four variants were defined for the gene 3 product, subtypes 3a, 3b, 3c, and 3d that differed in both the sequence of the third membrane spanning segment of the fourth repeat unit (IVS3) and in the size of the linker between this and the fourth membrane spanning segment (IVS4). Three CaCh 2 variants were cloned, subtypes 2a, 2c, and 2d, that are homologous to the a, c, and d variants of CaCh 3. For the skeletal muscle calcium channel only two variants were isolated. They are homologous to those of the a and c subtypes of CaCh 2 or 3, in that they differ only in the size of the IVS3 to IVS4 linker. These results demonstrate that calcium channel diversity is created by both the expression of distinct genes and the alternate splicing of these genes.
Expression regulated by
Comment
Ovarian localization
Comment
This gene is eXPRESSED IN HEART, OVARY, PANCREATIC
BETA-CELLS AND IN THE BRAIN.