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This Article Full Text Full Text (PDF) All Versions of this Article: 297/2/H680    most recent 00109.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Google Scholar Articles by Cheng, X. Articles by Jaggar, J. H. PubMed PubMed Citation Articles by Cheng, X. Articles by Jaggar, J. H.

Alternative splicing of Ca_v1.2 channel exons in smooth muscle cells of resistance-size arteries generates currents with unique electrophysiological properties

Departments of ¹Physiology and ²Pharmacology, University of Tennessee Health Science Center, Memphis, Tennessee

Submitted 30 January 2009 ; accepted in final form 1 June 2009

Voltage-dependent calcium (Ca²⁺, Ca_V1.2) channels are the primary Ca²⁺ entry pathway in smooth muscle cells of resistance-size (myogenic) arteries, but their molecular identity remains unclear. Here we identified and quantified Ca_V1.2 ₁-subunit splice variation in myocytes of rat resistance-size (100–200 µm diameter) cerebral arteries. Full-length clones containing either exon 1b or the recently identified exon 1c exhibited additional primary splice variation at exons 9*, 21/22, 31/32, and ± 33. Real-time PCR confirmed the findings from full-length clones and indicated that the major Ca_V1.2 variant contained exons 1c, 8, 21, and 32+33, with 57% containing 9*. Exon 9* was more prevalent in clones containing 1c (72%) than in those containing 1b (33%), suggesting exon-selective combinatorial splicing. To examine the functional significance of this splicing profile, membrane currents produced by each of the four exon 1b/c/ ± 9* variants were characterized following transfection in HEK293 cells. Exon 1c and 9* caused similar hyperpolarizing shifts in both current-voltage relationships and voltage-dependent activation of currents. Furthermore, exon 9* induced a hyperpolarizing shift only in the voltage-dependent activation of channels containing exon 1b, but not in those containing exon 1c. In contrast, exon 1b, 1c, or +9* did not alter voltage-dependent inactivation. In summary, we have identified the Ca_V1.2 ₁-subunit splice variant population that is expressed in myocytes of resistance-size arteries and the unique electrophysiological properties of recombinant channels formed by exon 1 and 9* variation. The predominance of exon 1c and 9* in smooth muscle cell Ca_V1.2 channels causes a hyperpolarizing shift in the voltage sensitivity of currents toward the physiological arterial voltage range.

voltage-dependent calcium channel; myogenic artery; cloning; ribonucleic acid splicing

This article has been cited by other articles:

				M. A. Nystoriak, K. Murakami, P. L. Penar, and G. C. Wellman Cav1.2 splice variant with exon 9* is critical for regulation of cerebral artery diameter Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1820 - H1828. [Abstract] [Full Text] [PDF]