Frequency- and Time-Dependent Effects of Fendiline on Action Potentials of Guinea Pig Papillary Muscle

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The action of fendiline on cardiac electrical activity was investigated in guinea pig papillary muscle by monitoring frequency− and time−dependent changes in membrane potential, action potential(AP)configuration and conduction velocity.Isolated guinea pig papillary muscles driven at 0.1 to 3 Hz showed a concentration−dependent reduction of + Vmax, overshoot, and AP duration at −20mV(APD20)in the presence of fendiline(1−320μM), reflecting inhibition of Na+ and L−type Ca2+ channels, respectively.No significant change in resting potential and AP duration at 90% repolarization(APD90)were observed.Inhibition of + Vmax and APD20 was more prominent at higher frequency of stimulation(2 Hz)than at lower ones(0.2 Hz), demonstrating frequency−dependent block of Na+ and Ca2+ channels including an open channel block.A good relationship between changes in + Vmax and APD20 suggested some commonality in the mechanism of inhibition of Na+ and Ca2+ channels by fendiline.Time−dependence of effects of fendiline, observed in presence of bolus dose(200μM), showed an earlier onset of inhibition of + Vmax and APD20, particularly at higher frequencies.Missed beats and conduction block also appeared earlier in preparations driven at higher frequency.These findings suggest a frequency−dependent(and open channel)block of Na+ and Ca2+ channels by fendiline, leading to inhibition of fast and slow conduction in addition to its reported inactivated Ca2+ channel block.
社団法人日本薬理学会の論文
2000-07-01

Frequency- and Time-Dependent Effects of Fendiline on Action Potentials of Guinea Pig Papillary Muscle

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