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

Abstract

Experiments were performed in bovine chromaffin cells in short term primary culture. Tetrandrine is a plant alkaloid from the chinese medical herb Stefania tetrandra. The aim of the present study was to investigate the mechanisms by which tetrandrine interacts with calcium signalling and to provide a quantitative description of effects. Tetrandrine blocked voltage-operated calcium channel currents concentration-dependently as shown in whole cell patch-clamp recordings. The blockade of calcium channels reduced the potassium-stimulated catecholamine release. Besides, the drug increased the spontaneous (not stimulated) release of catecholamines in the presence of extracellular calcium. Measurements of intracellular calcium levels [Ca]i showed a calcium release from intracellular stores by tetrandrine. This tetrandrine-induced [Ca]i elevation was higher in calcium containing as compared to calcium free solution. Tetrandrine effects partially overlap with those of thapsigargin, 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 blocking endoplasmic and other calcium pumps.