Alternative products:Additional isoforms seem to exist. Exons 8A , 21 , 22 , 31 , 32 , 33 , 40B , 43A , 41A and 45 are alternatively spliced in a variety of combinations. Experimental confirmation may be lacking for some isoforms ,Disease:Defects in CACNA1C are the cause of Brugada syndrome type 3 (BRS3) [MIM:611875]. BRS3 is a heart disease characterized by the association of Brugada syndrome with shortened QT intervals. Brugada syndrome is a tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG) . It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs (called ventricular fibrillation) , the individual will faint and may die in a few minutes if the heart is not reset. ,Disease:Defects in CACNA1C are the cause of Timothy syndrome (TS) [MIM:601005]. TS is a disorder characterized by multiorgan dysfunction including lethal arrhythmias , webbing of fingers and toes , congenital heart disease , immune deficiency , intermittent hypoglycemia , cognitive abnormalities and autism. ,Domain:Binding of intracellular calcium through the EF-hand motif inhibits the opening of the channel. ,Domain:Each of the four internal repeats contains five hydrophobic transmembrane segments (S1 , S2 , S3 , S5 , S6) and one positively charged transmembrane segment (S4) . S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position. ,Function: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. The various isoforms display marked differences in the sensitivity to DHP compounds. ,PTM:Phosphorylation by PKA activates the channel. ,similarity:Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. ,subunit: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. Interacts with CACNA2D4. ,tissue specificity:Expressed in brain , heart , jejunum , ovary , pancreatic beta-cells and vascular smooth muscle. Overall expression is reduced in atherosclerotic vascular smooth muscle. ,
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