Influence of Ca++-channel blocking agents on calcium transients and tension development in isolated mammalian heart muscle.

The Ca++-sensitive bioluminescent protein aequorin was used to detect cytoplasmic Ca++ transients in dog Purkinje strands and cat papillary muscles. Isometric tension development was recorded in both preparations, and transmembrane potential was monitored in the Purkinje strands. Voltage-clamp studies were carried out on some of the Purkinje strands. The aequorin signal of the Purkinje strand normally consists of two readily discernible components, which we have provisionally attributed to the entry of Ca++ through the surface membrane, and to the release of Ca++ from intracellular stores. D600 and verapamil reduced or eliminated both of these components, as they did the net inward current in fibers depolarized from a holding potential of -45 mV. In cat papillary muscles D600, verapamil, nifedipine, diltiazem, and perhexiline all had qualitatively similar effects on the aequorin signals and contractions. The effects of these agents differed from those of reduced [Ca++] in two important respects: the relation between light intensity and tension development was altered, and the mechanical contraction was abbreviated by the Ca++ channel blockers. These changes persist when the depressant effects of the Ca++ channel blockers are offset by elevations of [Ca++]o; they probably reflect a reduction in the Ca++ sensitivity of the myofilaments.