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Redox modulation of L-type calcium channels in ferret ventricular myocytes. Dual mechanism regulation by nitric oxide and S-nitrosothiols
The effects of NO-related activity and cellular thiol redox state on basal L-type calcium current, ICa,L, in ferret right ventricular myocytes were studied using the patch clamp technique. SIN-1, which generates both NO. and O2-, either inhibited or stimulated ICa,L. In the presence of superoxide di...
Formato: | Texto |
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Lenguaje: | English |
Publicado: |
The Rockefeller University Press
1996
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2229328/ https://www.ncbi.nlm.nih.gov/pubmed/8894977 |
Sumario: | The effects of NO-related activity and cellular thiol redox state on basal L-type calcium current, ICa,L, in ferret right ventricular myocytes were studied using the patch clamp technique. SIN-1, which generates both NO. and O2-, either inhibited or stimulated ICa,L. In the presence of superoxide dismutase only inhibition was seen. 8-Br- cGMP also inhibited ICa,L, suggesting that the NO inhibition is cGMP- dependent. On the other hand, S-nitrosothiols (RSNOs), which donate NO+, stimulated ICa,L. RSNO effects were not dependent upon cell permeability, modulation of SR Ca2+ release, activation of kinases, inhibition of phosphatases, or alterations in cGMP levels. Similar activation of ICa,L by thiol oxidants, and reversal by thiol reductants, identifies an allosteric thiol-containing "redox switch" on the L-type calcium channel subunit complex by which NO/O2- and NO+ transfer can exert effects opposite to those produced by NO. In sum, our results suggest that: (a) both indirect (cGMP-dependent) and direct (S-nitrosylation/oxidation) regulation of ventricular ICa,L, and (b) sarcolemma thiol redox state may be an important determinant of ICa,L activity. |
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