Contraction in voltage-clamped, internally perfused single heart cells.

We studied contraction in single voltage-clamped, internally perfused myocytes isolated from guinea pig ventricles. The microscopic appearance of the cell was observed and recorded with a television system, while contractile shortening was measured 1,000 times/s using a linear photodiode array. Uniform, synchronous sarcomere shortening occurred in response to depolarizations that triggered a slow inward current (Isi). Changes in Isi caused by altering the amplitude of the voltage step, the extracellular [Ca2+], or the holding potential were accompanied by immediate parallel changes in the extent and velocity of shortening. In particular, twitch shortening during depolarization was immediately decreased when large voltage steps decreased Isi, and was eliminated by depolarizations that exceeded +75 mV, the apparent reversal potential for Ca2+. In these cases, shortening was associated with the tail current during repolarization. Increases in the amplitude, duration, and the rate of the depolarizing step increased the extent and speed of sarcomere shortening over the course of four to five contractions without a simultaneous parallel increase of Isi. Large prolonged depolarizations caused an asynchronous, nonuniform, oscillatory shortening of the cell and potentiated future twitch contractions. Increases in the duration of the depolarizing step immediately prolonged contraction; otherwise, interventions that altered the extent, velocity, and time course of shortening in intact, nonperfused cells did not affect the time course of the contraction in the internally perfused single cells. Our results provide direct support for the hypothesis that Isi both induces and grades the size of the Ca2+ release from the sarcoplasmic reticulum of intact cardiac muscle. In addition, a separate, depolarization-dependent process unrelated to Isi grades the size of contraction, presumably by modulating Ca2+ accumulation in the intracellular stores, and affects its time course.