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

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Abstract
1 The ryanodine-sensitive component (RSC) of contraction electrically induced in the presence of A23187 (10−6 M) and isoprenaline (5 × 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 late component. 5 RSC produced by A23187 was not affected by blocking Na channel activation with tetrodotoxin (6 × 10−6 M). 6 In current and voltage clamp experiments, this RSC was inhibited by reducing the resting and the holding potentials in much the same way as observed on the preparations depolarized by increasing [K+]o. Such dependence on voltage was not observed with either the slow action potential or the slow Ca inward current. 7 These results suggest that the dependence of RSC on resting potentials is not due to the changes in the fast Na and the slow Ca inward currents. The present RSC via ryanodine-sensitive internal Ca release may be mainly triggered by a mechanism different from Ca influx through slow channels.

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