Sympathetic regulation of cardiac calcium current is due exclusively to cAMP-dependent phosphorylation
| Autor: | P F Méry, H C Hartzell, Szabo G, Rodolphe Fischmeister |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Nervous system
medicine.medical_specialty Sympathetic nervous system Sympathetic Nervous System G protein Guinea Pigs Stimulation Biology GTP-Binding Proteins Internal medicine Cyclic AMP medicine Animals Direct pathway of movement Patch clamp Phosphorylation Protein Kinase Inhibitors Multidisciplinary Isoproterenol Heart 3-Pyridinecarboxylic acid 1 4-dihydro-2 6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)- Methyl ester Phosphoproteins Myocardial Contraction Rats Endocrinology medicine.anatomical_structure cardiovascular system Calcium Calcium Channels Ion Channel Gating Acetylcholine medicine.drug |
| Zdroj: | Nature. 351:573-576 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/351573a0 |
| Popis: | THE positive inotropic effect of the sympathetic nervous system on the heart is partly mediated by an increase in the voltage-gated Ca2+ current (Ica) This increase is generally attributed to β-adrenergic receptor-stimulated cyclic AMP-dependent phos-phorylation of the Ca2+ channel1,2. It has been suggested that cAMP-dependent phosphorylation cannot explain all the effects of β-adrenergic agonists on ICa and that a parallel membrane-delimited pathway involving the 'direct' action of the G protein Gs also stimulates ICa (refs 3–7). A precedent exists for such a membrane-delimited pathway in the activation of a K+ channel by acetylcholine in heart1,8. A membrane-delimited pathway for stimulation of ICa might be important in rapid beat-to-beat regulation of contraction by the sympathetic nervous system9, because isoproterenol may produce a biphasic increase in ICa with the rapid phase (τ = 150 ms) putatively mediated by the direct pathway and the slow phase (τ = 35s) by cAMP-dependent phosphorylation. Here we report that in frog, rat, and guinea pig ventricular myocytes ICa increases slowly and monophasically in response to isoproterenol. The increase is completely blocked by inhibitors of cAMP-dependent phosphorylation. Furthermore, the time course of the increase in ICa closely parallels the increase in contractile force produced by sympathetic nerve stimulation. These data refute earlier suggestions that regulation of Ca2+ channels by the sym-pathetic nervous system involves or requires a direct G-protein pathway. |
| Databáze: | OpenAIRE |
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