Regulation of Cloned Cardiac L-type Calcium Channels by cGMP-dependent Protein Kinase
| Autor: | Dennis Wray, D. J. Gawler, Hugh A. Pearson, V A Porter, Nigel Hodson, Carol J. Milligan, Lin-Hua Jiang |
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| Rok vydání: | 2000 |
| Předmět: |
DNA
Complementary Indoles Patch-Clamp Techniques Calcium Channels L-Type Microinjections Xenopus Molecular Sequence Data Gi alpha subunit Carbazoles chemistry.chemical_element Biology Calcium N-type calcium channel Biochemistry SCN3A Alkaloids Cyclic GMP-Dependent Protein Kinases Animals L-type calcium channel Amino Acid Sequence Enzyme Inhibitors Phosphorylation Cyclic GMP Molecular Biology Myocardium Calcium channel Cell Biology Molecular biology R-type calcium channel chemistry Mutation Oocytes Rabbits Protein Kinases cGMP-dependent protein kinase |
| Zdroj: | Journal of Biological Chemistry. 275:6135-6143 |
| ISSN: | 0021-9258 |
| Popis: | We have studied the effect of 8-bromo-cyclic GMP (8-Br-cGMP) on cloned cardiac L-type calcium channel currents to determine the site and mechanism of action underlying the functional effect. Rabbit cardiac alpha(1C) subunit, in the presence or absence of beta(1) subunit (rabbit skeletal muscle) or beta(2) subunit (rat cardiac/brain), was expressed in Xenopus oocytes, and two-electrode voltage-clamp recordings were made 2 or 3 days later. Application of 8-Br-cGMP caused decreases in calcium channel currents in cells expressing the alpha(1C) subunit, whether or not a beta subunit was co-expressed. No inhibition of currents by 8-Br-cGMP was observed in the presence of the protein kinase G inhibitor KT5823. Substitutions of serine residues by alanine were made at residues Ser(533) and Ser(1371) on the alpha(1C) subunit. As for wild type, the mutant S1371A exhibited inhibition of calcium channel currents by 8-Br-cGMP, whereas no effect of 8-Br-cGMP was observed for mutant S533A. Inhibition of calcium currents by 8-Br-cGMP was also observed in the additional presence of the alpha(2)delta subunit for wild type channels but not for the mutant S533A. These results indicate that cGMP causes inhibition of L-type calcium channel currents by phosphorylation of the alpha(1C) subunit at position Ser(533) via the action of protein kinase G. |
| Databáze: | OpenAIRE |
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