Inactivation of the cardiac ryanodine receptor calcium release channel by nitric oxide.
We have recently reported [Mészáros L.G., Minarovic I., Zahradníková A. Inhibition of the skeletal muscle ryanodine receptor calcium release channel by nitric oxide. FEBS Lett 1996; 380: 49-52] 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.
Zahradníková
A
A
Department of Physiology & Endocrinology, Medical College of Georgia, Augusta 30912, USA.
Minarovic
I
I
Venema
R C
RC
Mészáros
L G
LG
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D004285:Dogs; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*
D015220:Calcium Channels; D019837:Ryanodine Receptor Calcium Release Channel; D009569:Nitric Oxide