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PMID: 8894977 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Redox modulation of L-type calcium channels in ferret ventricular myocytes. Dual mechanism regulation by nitric oxide and S-nitrosothiols.

The Journal of general physiology ·Vol. 108 ·No. 4 ·1996-10-00 ·Pages 277-93

Campbell DL, Stamler JS, Strauss HC

Abstract

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.

MeSH Terms
Animals Calcium Channels/drug effects,metabolism Extracellular Space/metabolism Ferrets Heart Ventricles Male Molsidomine/analogs & derivatives,pharmacology Myocardium/cytology,metabolism Nitric Oxide/physiology Nitroso Compounds/metabolism Oxidation-Reduction Patch-Clamp Techniques Sulfhydryl Compounds/physiology
Chemicals
Calcium Channels Nitroso Compounds Sulfhydryl Compounds Nitric Oxide linsidomine Molsidomine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Campbell D L
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Stamler J S
Strauss H C
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Article Info
Journal
The Journal of general physiology
Abbr.
J Gen Physiol
ISSN
0022-1295
DOI
10.1085/jgp.108.4.277
Published
1996-10-00
Pages
277-93
Language
English
Region
United States
NLM ID
2985110R
PMCID
PMC2229328
Subset
IM
Grants
NHLBI NIH HHS · HL02582 · United States
NHLBI NIH HHS · HL19216 · United States
NHLBI NIH HHS · HL54314 · United States
External Links
PubMed source DOI: 10.1085/jgp.108.4.277 PMC Full Text View journal details
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