Rao_1987_J.Pharmacol.Exp.Ther_243_775

The mechanism of the twitch potentiating action of pumiliotoxin-B (PTX-B), an indolizidine alkaloid from the skin of the frog Dendrobates pumilio, was studied on frog skeletal muscles. In the presence of PTX-B, a single stimulus to the muscle produced either a burst of repetitive action potentials superimposed on a depolarizing afterpotential or a single potential with a prolonged afterpotential at junctional as well as extrajunctional regions of the frog skeletal muscle fibers. The alkaloid did not cause repetitive activity in quiescent cells or spontaneous contractions. The duration of the burst of action potentials was related inversely and the amplitude and duration of postburst depolarizing after-potential was related directly to the concentration of PTX-B. The typical pattern of repetitive action potentials and postburst depolarization induced by PTX-B could be mimicked by depolarizing the muscle membrane with current pulses of long duration (150-470 ms). Lowering the external calcium or sodium concentration reduced the ability of PTX-B to initiate repetitive action potentials, whereas a low external chloride concentration had no effect. The frequency of MEPPs evoked by potassium, but not the spontaneous MEPP frequency, was increased by PTX-B, suggesting a selective effect on evoked transmitter release. PTX-B evoked repetitive EPPs in response to a single stimulus applied to the nerve, which was dependent upon the external calcium ion concentration. The amplitudes of EPPs in the train were facilitated, and their amplitude increased linearly at the lowest calcium concentration, but not at concentrations from 0.45 to 1.8 mM.(ABSTRACT TRUNCATED AT 250 WORDS)