Mechanism of activation of the tonic component of contraction in myocytes of guinea pig heart

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Abstract

Aim

Contractions of myocytes of guinea pig heart consist of a phasic component relaxing independently on the voltage and a tonic component relaxing upon repolarization. We found previously that Ca2+ activating the tonic component is released from the sarcoplasmic reticulum. In this study, we analysed the mechanism of activation and maintenance of this release.

Methods

Experiments were performed at 37 °C in ventricular myocytes of guinea pig heart. Voltage-clamped myocytes were stimulated by the pulses of the duration of 300 ms to 15–45 s from the holding potential of −40 to +5 mV. [Ca2+]i was monitored as fluorescence of Indo-1 and contractions were recorded with the TV edge-tracking system.

Results

Myocytes responded to the short and long pulses with phasic contraction or Ca2+ transient followed by the sustained contraction or increase in [Ca2+]i. Repolarization brought about relaxation. 10 mmol L−1 Ni2+ blocking Na+/Ca2+ exchange superfused during the tonic component increased its amplitude. Superfusion of Ca2+-free solution during sustained contraction brought about relaxation both in normal cells and in cells superfused with Ni2+ despite preserved sarcoplasmic reticulum Ca2+ content assessed with caffeine spritz. Relaxing effect of Ca2+-free solution was not affected by carboxyeosin, a blocker of sarcolemmal Ca2+-ATPase. Tonic component of contraction and of Ca2+ transient was inhibited by 200 μmol L−1 ryanodine, a blocker of Ca2+ release channels of the sarcoplasmic reticulum and by 20 μmol L−1 nifedipine, a blocker of L-type ICa.

Conclusion

Tonic component of contraction results from Ca2+ release via the sarcoplasmic reticulum Ca2+ channels activated by sustained, nifedipine-sensitive and Ni2+-insensitive Ca2+ influx. Alternatively, the SR Ca2+ release is activated by voltage, the dihydropyridine receptors acting like voltage sensors.

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