Cadmium block of isometric contractions of isolated bullfrog atrial cells

Abstract

We studied the effect of cadmium, verapamil, and quinacrine on the force of contraction (Fp) of isolated, single, field-stimulated bullfrog atrial cells. All agents were applied or removed rapidly (t1/2 approximately 15 ms) to minimize intracellular concentration changes other than intracellular calcium concentration. Two components of twitch force were observed, one blocked by micromolar Cd2+ and the other by millimolar Cd2+. The two contributed about equally to the activation of the twitch. The "cadmium-sensitive" portion of force (that affected by [Cd] less than or equal to 100 microM) had a K1/2 approximately 1 microM, was identical in magnitude to, and not additive with, a "verapamil-sensitive" (10 microM) component of force, was most strongly affected by 50-ms pulses of Cd2+ when they were applied in the mechanical latent period, and was potentiated by catecholamines. The cadmium-insensitive portion of force was abolished by the removal of extracellular calcium and was greatly potentiated by quinacrine (3 or 10 microM), a blocker of Na-Ca exchange. The results are consistent with the idea that activating calcium enters the cell via both an inactivating cadmium-sensitive L-type channel and a noninactivating cadmium-insensitive mechanism that is not Na-Ca exchange and leaves the cell via Na-Ca exchange.