EFFECTS OF TETRANDRINE ON CALCIUM-CHANNEL CURRENTS OF BOVINE CHROMAFFIN CELLS

Calcium channel currents of bovine chromaffin cells are blocked by the bis-benzyl-isoquinoline alkaloid tetrandrine, which is isolated from the roots of the chinese medical herb Stephania tetrandra. The haIf-ma ximal inhibition (IC50) occurred at a concentration of about 10 mu M. Bovine chromaffin cells possess no low-voltage-activated, but differen t types of high-voltage activated calcium channel currents. Tetrandrin e blocks omega-conotoxin-sensitive N-type, dihydropyridine-sensitive L -type and omega-conotoxin- and dihydropyridine-insensitive calcium cha nnel currents of chromaffin cells. The I/V relationship is not shifted by tetrandrine, indicating that the block is not voltage-dependent, A fter tetrandrine application the currents become transient in a depola rization- and a concentration-dependent manner. Tetrandrine blocks ope n calcium channels and the block is use-dependent. When the holding po tential returns to resting levels, the channels are unblocked in about 1 sec.