Inhibition of Ion Channels by Hirsutine in Rat Pheochromocytoma Cells

Effects of hirsutine, an alkaloid that produces a potent ganglion blocking effcct, were investigated using rat pheochromocytoma PC12 cells. Hirsutine (1 to 10μM) suppressed dopamine-release evoked by 100 μM nicotine. In voltage-clamped cells, hirsutine (1 to 10 μM) inhibited the inward current activated by 100 μM nicotine. Hirsutine’ was equipotent to hexamethonium in blocking the nicotine-activated current. The voltage-dependency of the nicotine activated current was not modified by hirsutine. Effects of hirustine on other ion channels were tested to determire its selectivity. Inward currents mediated through ATP-activated channels were scarcely affected by hirsutine (up to 100 μM). However, hirustine (10μM) inhibited Ba currents passing through Ca channels and K currents activated by depolarizing voltage steps. The results suggest that hirsutine potently blocks nicotinic receptor-channels, but hirsutine also inhibits voltage-gated Ca and K channels. Roles of the inhibition of these channels in the pharmacological effects of hirsutine were discussed.