A novel CaV1.2 N terminus expressed in smooth muscle cells of resistance size arteries modifies channel regulation by auxiliary subunits

Xiaoyang Cheng, Jianxi Liu, Maria Asuncion-Chin, Eva Blaskova, John P. Bannister, Alejandro Dopico, Jonathan Jaggar

Research output: Contribution to journalArticle

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Abstract

Voltage-dependent L-type Ca2+ (CaV1.2) channels are the principal Ca2+ entry pathway in arterial myocytes. Ca V1.2 channels regulate multiple vascular functions and are implicated in the pathogenesis of human disease, including hypertension. However, the molecular identity of CaV1.2 channels expressed in myocytes of myogenic arteries that regulate vascular pressure and blood flow is unknown. Here, we cloned CaV1.2 subunits from resistance size cerebral arteries and demonstrate that myocytes contain a novel, cysteine rich N terminus that is derived from exon 1 (termed "exon 1c"), which is located within CACNA1C, the CaV1.2 gene. Quantitative PCR revealed that exon 1c was predominant in arterial myocytes, but rare in cardiac myocytes, where exon 1a prevailed. When co-expressed with α2δ subunits, CaV1.2 channels containing the novel exon 1c-derived N terminus exhibited: 1) smaller whole cell current density, 2) more negative voltages of half activation (V1/2,act) and half-inactivation (V 1/2,inact), and 3) reduced plasma membrane insertion, when compared with channels containing exon 1b. β1b and β2a subunits caused negative shifts in the V1/2,act and V 1/2,inact of exon 1b-containing CaV1.2α1/ α2δ currents that were larger than those in exon 1c-containing CaV1.2α12δ currents. In contrast, β3 similarly shifted V1/2,act and V1/2,inact of currents generated by exon 1b- and exon 1c-containing channels. β subunits isoform-dependent differences in current inactivation rates were also detected between N-terminal variants. Data indicate that through novel alternative splicing at exon 1, the Ca V1.2 N terminus modifies regulation by auxiliary subunits. The novel exon 1c should generate distinct voltage-dependent Ca2+ entry in arterial myocytes, resulting in tissue-specific Ca2+ signaling.

Original languageEnglish (US)
Pages (from-to)29211-29221
Number of pages11
JournalJournal of Biological Chemistry
Volume282
Issue number40
DOIs
StatePublished - Oct 5 2007

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Cell Size
Smooth Muscle Myocytes
Muscle
Exons
Arteries
Cells
Muscle Cells
Blood Vessels
Electric potential
Cerebral Arteries
Alternative Splicing
Cell membranes
Cardiac Myocytes
Cysteine
Protein Isoforms
Blood
Current density
Cell Count
Genes
Chemical activation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

A novel CaV1.2 N terminus expressed in smooth muscle cells of resistance size arteries modifies channel regulation by auxiliary subunits. / Cheng, Xiaoyang; Liu, Jianxi; Asuncion-Chin, Maria; Blaskova, Eva; Bannister, John P.; Dopico, Alejandro; Jaggar, Jonathan.

In: Journal of Biological Chemistry, Vol. 282, No. 40, 05.10.2007, p. 29211-29221.

Research output: Contribution to journalArticle

Cheng, Xiaoyang ; Liu, Jianxi ; Asuncion-Chin, Maria ; Blaskova, Eva ; Bannister, John P. ; Dopico, Alejandro ; Jaggar, Jonathan. / A novel CaV1.2 N terminus expressed in smooth muscle cells of resistance size arteries modifies channel regulation by auxiliary subunits. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 40. pp. 29211-29221.
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