Dissociation between force and [Ca2+](i) during extra systoles in guinea-pig ventricular muscle microinjected with fura-2

Thin trabeculae were dissected from the right ventricle of guinea-pig heart and stimulated to contract isometrically at 0.5 Hz (26 degrees C). Rapid a nd transient changes of force were obtained by inducing three extra systole s (ES1-3) at 450-ms intervals. The two regular contractions (P1-2) followin g (ES1-3) were potentiated. Fura-2 salt was microinjected into the preparat ion to monitor intracellular calcium ([Ca2+](i)). Three distinct phases of [Ca2+](i) were seen: (1) a rapid rising phase to about 200 nmol L-1. (2) a slower rising phase to a peak at 400 nmol L-1, and (3) a slow decline to ab out 50 nmol L-1. During ES1, there was a discrepancy between force, which d ecreased, and peak [Ca2+](i), which increased to 600 nmol L-1. It is likely that the increased [Ca2+](i) during the extra systoles reflects increased sarcolemmal calcium inflow, causing post-extra-systolic potentiation. Ryano dine (1-2 mu M) was added to inhibit the intracellular calcium release and thus reduce the intracellular [Ca2+](i) gradients following excitation. Rya nodine inhibited phase 1 of [Ca2+](i) and abolished post-extra-systolic pot entiation. There was a close relationship between dF/dt and [Ca2+](i) with ryanodine during control and ES1-3. It is likely that fura-2 reports a spat ially averaged [Ca2+](i) and that phase 1 of the signal therefore apparentl y underestimates activator calcium in the close vicinity of the contractile elements.