A potent factor in extracts of the skin of the Australian frog, Pseudophryne coriacea--III. Potentiation of contractions elicited in avian and mammalian isolated skeletal muscle preparations by direct and indirect electrical stimulation.

Extracts of the skin of the Australian frog Pseudophryne coriacea displayed a striking potentiating effect on contractions evoked in isolated skeletal muscle preparations of mammals (phrenic nerve diaphragm) and birds (chick biventer cervicis and semispinalis muscles) by indirect and direct electrical stimulation. There was both a conspicuous increase in the amplitude of the twitch, up to 10-fold, and a remarkable prolongation of the duration of the twitch. The effect was dose- and frequency-dependent. In the presence of the extract, fusion of twitches after tetanic stimulation occurred earlier. No tachyphylaxis upon repeated stimulation by the extract was observed and the response to large doses persisted, declining slowly, for hours. These effects must be ascribed to an alkaloid related in structure to pumiliotoxin B. Response to the extract of Pseudophryne coriacea by indirectly-stimulated preparations was potentiated by physostigmine and blocked by tubocurarine and alpha-bungarotoxin, demonstrating that in these preparations the extract acted pre-synaptically to facilitate the release of acetylcholine from motor nerve endings. However, the extract of Pseudophryne coriacea displayed equally potent effects in directly stimulated preparations, insensitive to physostigmine and to blockers of nicotinic acetylcholine receptors, indicating a direct action on the skeletal muscle. It is suggested that, like pumiliotoxin B, the Pseudophryne coriacea alkaloid may interfere in the regulation of calcium channels in both nerve and muscle fibres.