Effects of flunarizine on the distribution of calcium in vascular smooth muscle.

Exposure of depolarized caudal artery preparations of the rat to various calcium concentrations evoked sustained contractions of the smooth muscle in a dose-dependent way. Flunarizine was shown to suppress this sustained muscle contraction. Experiments were undertaken to determine the subcellular site where flunarizine interferes with the calcium-induced contractile process. The subcellular distribution of calcium was assessed by electron microscopy, using a combined oxalate-pyroantimonate method. In depolarized strips precipitated calcium was mainly distributed over the contractile elements and the microvesicles lining the cell membrane. When flunarizine was added to the preparation, the precipitate was predominantly confined to the extracellular space, whereas only spotty precipitates were seen in mitochondria and sarcoplasmic reticulum. The myofibrils were almost free of deposits. Without previous depolarization, the smooth muscle cells demonstrated a moderate amount of precipitate over the mitochondria, nuclei, sarcoplasmic vesicles, plasmalemmal microvesicles and myofibrils. In these conditions neither the amount nor the intracellular distribution of the precipitate was influenced by the addition of flunarizine. These observations suggest that flunarizine interfers with the entry of calcium at the plasma membrane level, but only in conditions where the influx of the ion is stimulated.