Smooth Muscle-selective Alternatively Spliced Exon Generates Functional Variation in Cav1.2 Calcium Channels
Voltage-gated calcium channels play a major role in many important processes including muscle contraction, neurotransmission, excitation-transcription coupling, and hormone secretion. To date, 10 calcium channel α1-subunits have been reported, of which four code for L-type calcium channels. In our p...
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Published in | The Journal of biological chemistry Vol. 279; no. 48; pp. 50329 - 50335 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
26.11.2004
American Society for Biochemistry and Molecular Biology |
Subjects | |
Online Access | Get full text |
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Summary: | Voltage-gated calcium channels play a major role in many important processes including muscle contraction, neurotransmission, excitation-transcription coupling, and hormone secretion. To date, 10 calcium channel α1-subunits have been reported, of which four code for L-type calcium channels. In our previous work, we uncovered by transcript-scanning the presence of 19 alternatively spliced exons in the L-type Cav1.2 α1-subunit. Here, we report the smooth muscle-selective expression of alternatively spliced exon 9* in Cav1.2 channels found on arterial smooth muscle. Specific polyclonal antibody against exon 9* localized the intense expression of 9*-containing Cav1.2 channels on the smooth muscle wall of arteries, but the expression on cardiac muscle was low. Whole-cell patch clamp recordings of the 9*-containing Cav1.2 channels in HEK293 cells demonstrated -9 and -11-mV hyperpolarized shift in voltage-dependent activation and current-voltage relationships, respectively. The steady-state inactivation property and sensitivity to blockade by nifedipine of the ±exon 9* splice variants were, however, not significantly different. Such cell-selective expression of an alternatively spliced exon strongly indicates the customization and fine tuning of calcium channel functions through alternative splicing of the pore-forming α1-subunit. The generation of proteomic variations by alternative splicing of the calcium channel Cav1.2 α1-subunit can potentially provide a flexible mechanism for muscle or neuronal cells to respond to various physiological signals or to diseases. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M409436200 |