The Relation Between Membrane Potential, Membrane Currents and Activation of Contraction in Ventricular Myocardial Fibres

1. Membrane currents and contractile responses have been measured in ventricular myocardial preparations under voltage clamp conditions.2. In Tyrode solution, steady-state contraction was obtained only after 5-8 depolarizations to a given potential level. The threshold of steady-state tension was identical to the potential where the calcium inward current, I(Ca), was activated (about -35 mV). Both thresholds were shifted in the same direction along the voltage axis and by the same amount by changing [Ca](o) or [Na](o). Maximum tension was obtained at inside positive potentials.3. The time courses of steady-state tension and of activation of I(Ca) were different by more than one order of magnitude in Tyrode solution. But in order to achieve any appreciable steady-state tension, I(Ca) had to flow during several identical depolarizations. Tension decreased again at potentials above E(Ca). This suggests that calcium inward current must flow in order to fill intracellular calcium stores from which calcium can be released by an unknown mechanism.4. The ability of a fibre bundle to contract again after a preceding twitch is greatly dependent on the membrane potential between two equal depolarizations. In Tyrode solutions with 1.8 and 7.2 mM-CaCl(2) half restoration of this ability occurred at -45 +/- 3 mV (+/- S.E. of mean) and -23 +/- 4 mV, respectively.5. In sodium-free bathing solutions, steady-state tension was attained upon the first depolarization provided I(Ca) was activated. Furthermore, at different potentials, the time courses of activation of tension and of activation of I(Ca) were identical, i.e. tension reached its maximum when I(Ca) was fully activated. This suggests that in sodium-free solutions the flow of calcium ions into the fibre directly activates contraction.