Voltage-dependence of ryanodine-sensitive component of contraction in A23187- and isoprenaline-treated cardiac muscles

British Journal of Pharmacology
N Kondo

Abstract

1. The ryanodine-sensitive component (RSC) of contraction electrically induced in the presence of A23187 (10(-6) M) and isoprenaline (5 x 10(-8) M) was investigated in guinea-pig papillary muscles that had been partially depolarized to various membrane potentials by increasing [K+]o, and current and voltage clamp techniques. 2. Two components of contraction were produced by A23187 and isoprenaline at a stimulation frequency of 0.2 Hz. The early component was sensitive to ryanodine (10(-6) M) (corresponding to RSC), while the late component was sensitive to nifedipine (10(-6) M). 3. In the presence of nifedipine, RSCs produced by these drugs were selectively observed. Under these conditions, RSCs were voltage-dependently inhibited by a reduction in resting potential that was brought about by increasing [K+]o (10-26 mM). The onset of inhibition of RSCs appeared at a resting potential between -75 and -70 mV, and almost complete inhibition was observed at a potential between -55 and -50 mV, indicating that RSCs produced by these drugs have the same voltage-dependence. 4. In the absence of nifedipine, this voltage-dependent inhibition was also observed on the early component of contraction produced by A23187 without affecting the la...Continue Reading

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