Inactivation of the cardiac ryanodine receptor calcium release channel by nitric oxide

Alexandra Zahradníková, Igor Minarovic, Richard C. Venema, László G. Mészáros

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

We have recently reported that nitric oxide (NO) reduces the activity of the skeletal muscle ryanodine receptor Ca2+ release channel (RyRC), a principal component of the excitation-contraction coupling machinery in striated muscles. Since (i) as shown here, we have obtained evidence which indicates that the NO synthase (eNOS) of cardiac muscle origin co-purified with RyRC-containing sarcoplasmic reticulum (SR) fractions; and (ii) the effects of NO donors on the release channel, as well as on cardiac function, appear somewhat contradictory, we have made an attempt to investigate the response of the cardiac RyRC to NO that is generated in situ from L-arginine in the NOS reaction. We found that L-arginine-derived NO inactivates Ca2+ release from cardiac SR and reduces the steady-state activity (i.e. open probability) of single RyRCs fused into a planar lipid bilayer. This reduction was prevented by NOS inhibitors and the NO quencher hemoglobin and was reversed by 2-mercaptoethanol. We thus conclude that: (i) in isolated SR preparations, it is possible to assess the effects of NO that is generated from L-arginine in the NOS reaction; and (ii) cardiac RyRc responds to NO in a manner which is identical to that we have previously found with the skeletal channel. These findings suggest that the direct modulation of the RyRC by NO is a signaling mechanism which likely participates in earlier demonstrated NO-induced myocardial contractility changes.

Original languageEnglish (US)
Pages (from-to)447-453
Number of pages7
JournalCell Calcium
Volume22
Issue number6
DOIs
StatePublished - Dec 1997

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Inactivation of the cardiac ryanodine receptor calcium release channel by nitric oxide'. Together they form a unique fingerprint.

  • Cite this

    Zahradníková, A., Minarovic, I., Venema, R. C., & Mészáros, L. G. (1997). Inactivation of the cardiac ryanodine receptor calcium release channel by nitric oxide. Cell Calcium, 22(6), 447-453. https://doi.org/10.1016/S0143-4160(97)90072-5