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

102 Citations (Scopus)

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 - Jan 1 1997

Fingerprint

Ryanodine Receptor Calcium Release Channel
Nitric Oxide
Sarcoplasmic Reticulum
Arginine
Excitation Contraction Coupling
Striated Muscle
Nitric Oxide Donors
Mercaptoethanol
Lipid Bilayers
Nitric Oxide Synthase
Myocardium
Skeletal Muscle

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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

Inactivation of the cardiac ryanodine receptor calcium release channel by nitric oxide. / Zahradníková, Alexandra; Minarovic, Igor; Venema, Richard C; Mészáros, László G.

In: Cell Calcium, Vol. 22, No. 6, 01.01.1997, p. 447-453.

Research output: Contribution to journalArticle

Zahradníková, A, Minarovic, I, Venema, RC & Mészáros, LG 1997, 'Inactivation of the cardiac ryanodine receptor calcium release channel by nitric oxide', Cell Calcium, vol. 22, no. 6, pp. 447-453. https://doi.org/10.1016/S0143-4160(97)90072-5
Zahradníková, Alexandra ; Minarovic, Igor ; Venema, Richard C ; Mészáros, László G. / Inactivation of the cardiac ryanodine receptor calcium release channel by nitric oxide. In: Cell Calcium. 1997 ; Vol. 22, No. 6. pp. 447-453.
@article{defd8422ca364cbbad1b06edd74b1389,
title = "Inactivation of the cardiac ryanodine receptor calcium release channel by nitric oxide",
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.",
author = "Alexandra Zahradn{\'i}kov{\'a} and Igor Minarovic and Venema, {Richard C} and M{\'e}sz{\'a}ros, {L{\'a}szl{\'o} G.}",
year = "1997",
month = "1",
day = "1",
doi = "10.1016/S0143-4160(97)90072-5",
language = "English (US)",
volume = "22",
pages = "447--453",
journal = "Cell Calcium",
issn = "0143-4160",
publisher = "Churchill Livingstone",
number = "6",

}

TY - JOUR

T1 - Inactivation of the cardiac ryanodine receptor calcium release channel by nitric oxide

AU - Zahradníková, Alexandra

AU - Minarovic, Igor

AU - Venema, Richard C

AU - Mészáros, László G.

PY - 1997/1/1

Y1 - 1997/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0031461380&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031461380&partnerID=8YFLogxK

U2 - 10.1016/S0143-4160(97)90072-5

DO - 10.1016/S0143-4160(97)90072-5

M3 - Article

VL - 22

SP - 447

EP - 453

JO - Cell Calcium

JF - Cell Calcium

SN - 0143-4160

IS - 6

ER -