| Autor: |
Palygin, Ojeg A., Pettus, Janette M., Shibata, Erwin F. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Heart & Circulatory Physiology; Apr2008, Vol. 294 Issue 4, pH1693-H1699, 7p, 5 Graphs |
| Abstrakt: |
Cardiac sodium channels (voltage-gated Na~ channel subunit 1.5) reside in both the plasmalemma and membrane invaginations called caveolae. Opening of the caveolar neck permits resident channels to become functional. In cardiac myocytes, caveolar opening can be stimulated by applying 3-receptor agonists, which initiates an interaction between the stimulatory 0 protein subunit-a (Gsa) and caveolin-3. This study shows that, in adult rat ventricular myocytes, a functional G~a-caveolin-3 interaction occurs, even in the absence of the caveolin-binding seaquence motif of Gsa. Consistent with previous data, whole cell experiments conducted in the presence of intracellular PKA inhibitor stimulation with ~3-receptor agonists increased the sodium current (`Na) by 35.9 ± 8.6% (P < 0.05), and this increase was mimicked by application of G~a protein. Inclusion of anti-caveolin-3 antibody abolished this effect. These findings suggest that G~a and caveolin-3 are components of a PKA-independent pathway that leads to the enhancement of `Na. In this study, alanine scanning mutagenesis of G~a (40THR42), in conjunction with voltage-clamp studies, demonstrated that the histidine residue at position 41 of G~a (H41) is a critical residue for the functional increase of `Na. Protein interaction assays suggest that G~aFL (full length) binds to caveolin-3, but the enhancement of `Na is observed only in the presence of G~a H4l. We conclude that G~a H41 is a critical residue in the regulation of the increase in `Na in ventricular myocytes. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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