December 1, 2001AJP Heart and Circulatory Physiology61 citations
Positive and negative effects of nitric oxide on Ca2+sparks: influence of β-adrenergic stimulation
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Key Result
Nitric oxide (300 microM) decreased Ca2+ spark frequency during high beta-adrenergic stimulation but increased it during low stimulation in rat ventricular myocytes.
Structured PICO
P
Population
Rat ventricular myocytes
I
Intervention
Nitric oxide (spermine NONOate, 300 microM) combined with high or low concentrations of isoproterenol
C
Comparator
Different concentrations of isoproterenol without NO, or baseline
O
Outcome
Ca2+ spark frequency (CaSpF)surrogate
The net effect of nitric oxide on ryanodine receptor activity and calcium transients in ventricular myocytes can be reversed depending on the ambient level of beta-adrenergic activation.
Abstract
Nitric oxide (NO) can have a positive or negative effect on cardiac contractility and the ryanodine receptor (RyR). This dual effect has been explained as being dependent on the concentration of NO. We find that cellular RyR response to NO is also dependent on the degree of beta-adrenergic stimulation, and thus the state of protein kinase A activation. Ca(2+) spark frequency (CaSpF) in rat ventricular myocytes was used as an index of resting RyR activity. CaSpF response to beta-adrenergic stimulation was used as an index of protein kinase A activation. High concentration of isoproterenol, a beta-adrenergic agonist, caused a large increase in CaSpF; addition of NO (spermine NONOate, 300 microM) then caused a decrease in CaSpF. Low concentration of isoproterenol produced only a slight increase in CaSpF, but the same NO concentration now caused a large increase in CaSpF. A dual effect was also observed in twitch. Thus the net direction of the effects of NO on RyR activity and Ca(2+) transients (directly or by alteration of sarcoplasmic reticulum Ca(2+) load) can be reversed, depending on the ambient level of beta-adrenergic activation.