Myocytes of resistance‐size arteries express Ca V 1.2 channels with a novel N‐terminus

Abstract

Voltage-dependent L-type Ca2+ channels (CaV1.2) are the principal Ca2+ entry pathway in myocytes of small arteries that regulate vascular pressure and blood flow. However, the molecular identity of the pore-forming a1 subunit (CaV1.2) expressed in myocytes of myogenic arteries is unclear. Here, we cloned CaV1.2 subunits from rat resistance-sized cerebral arteries and found they contain a novel, cysteine rich N-terminus that derives from exon 1 (termed exon 1c), which is located within CACNA1C, the CaV1.2 gene. Another 5′ end sequence (exon 1b) identical to the brain CaV1.2 5′ end was also detected. Exon 1c was predominant in arterial myocytes, but barely present in cardiac myocytes where exon 1a prevailed. When co-expressed with a2d subunits, macroscopic currents generated from channels containing the exon 1c-derived N-terminus exhibited a smaller IBa density and more negative voltages of half activation (V1/2,act) and half inactivation (V1/2,inact) when compared with those containing exon 1b. Co-expression of ß subunits increased IBa density, caused hyperpolarizing shifts in V1/2,act and V1/2,inact, and eliminated differences observed when channels were expressed with only a2d. Our data indicate that modulation of CaV1.2 currents mediated by a novel CaV1.2 N-terminus may lead to tissue specific Ca2+ signaling in myocytes of resistance-size arteries.