Summary
This study was aimed to assess the relationship among the voltage-dependent processes underlying the excitation-contraction coupling, viz. force restitution (FR), transmembrane Ca fluxes and Ca release. The experiments (n=22) were performed on voltage-clamped dog trabeculae in which force and slow inward current were measured. Standard steady-state was achieved by clamp driving at 0.5 Hz, 300 ms, 70 mV depolarizing pulses from holding=resting potential at 30°C. Voltage and duration of single pulses and intervals in between were varied according to five protocols.
The voltage dependence of Ca release was tested by varying single pulses at equal steady-state, i.e., at equal Ca availability. Contractions could be elicited in absence of ICa (20–30 mV step) and in the presence of disproportionately small ICa (above 80 mV).
The voltage dependence of Ca availability for the release was tested by constant test pulses following either a variable conditioning clamp pulse or a period of rest at a variable voltage. After a low voltage pulse and, hence, depressed or absent ICa, the test contraction is diminished in presence of normal or even augmented Isi at any test interval (i.e., FR is depressed). Diminished Ca influx thus reduces the Ca availability of the subsequent beat. During prolonged depolarization (by 60 mV and more) a tonic response appears, but a phasic response cannot be elicited (FR is inhibited). Upon subsequent repolarization FR starts from zero and is significantly enhanced.
It is concluded that, during depolarization, Ca release channels are in an open state, thus allowing free recirculation of Ca, but no build-up of a sufficient Ca gradient at the release site.
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Bravený, P., Simurda, J. & Šimurdová, M. Voltage dependence of force- and slow inward current restitution in ventricular muscle. Basic Res Cardiol 87, 418–427 (1992). https://doi.org/10.1007/BF00795054
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DOI: https://doi.org/10.1007/BF00795054