BLOCKADE OF VOLTAGE-OPERATED CALCIUM CHANNELS, INCREASE IN SPONTANEOUS CATECHOLAMINE RELEASE AND ELEVATION OF INTRACELLULAR CALCIUM LEVELS IN BOVINE CHROMAFFIN CELLS BY THE PLANT ALKALOID TETRANDRINE

Experiments were performed in bovine chromaffin cells in short term pr imary culture. Tetrandrine is a plant alkaloid from the chinese medica l herb Stefania tetrandra. The aim of the present study was to investi gate the mechanisms by which tetrandrine interacts with calcium signal ling and to provide a quantitative description of effects. Tetrandrine blocked voltage-operated calcium channel currents concentration-depen dently as shown in whole cell patch-clamp recordings. The blockade of calcium channels reduced the potassium-stimulated catecholamine releas e. Besides, the drug increased the spontaneous (not stimulated) releas e of catecholamines in the presence of extracellular calcium. Measurem ents of intracellular calcium levels [Ca]i showed a calcium release fr om intracellular stores by tetrandrine. This tetrandrine-induced [Ca]i elevation was higher in calcium containing as compared to calcium fre e solution. Tetrandrine effects partially overlap with those of thapsi gargin, but tetrandrine has additional targets, since it increased [Ca ]i in cells pretreated with thapsigargin. We conclude that tetrandrine blocks voltage-operated calcium channels and increases [Ca]i by block ing endoplasmic and other calcium pumps.