State‐dependent action of grayanotoxin I on Na+ channels in frog ventricular myocytes

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Abstract
1 Distinct properties of grayanotoxin (GTX) among other lipid-soluble toxins were elucidated by quantitative analysis made on the Na+ channel in frog ventricular myocytes. 2 GTX-modified current (IGTX) was induced strictly in proportion to the open probability of Na+ channels during preconditioning pulses irrespective of its duration, amplitude or partial removal of inactivation by chloramine-T. This confirms that GTX binds to the Na+ channel exclusively in its open state, while batrachotoxin (BTX) was reported to be capable of modifying slow-inactivated Na+ channels, and veratridine exhibited voltage-dependent modification. 3 The GTX-modified channel did not show any inactivation property, which is different from reported results with veratridine and BTX. 4 Estimated unbinding rates of GTX were in reverse proportion to the activation curve of GTX-modified Na+ channels. This was not the previously reported case with veratridine. 5 A model including unbinding kinetics of GTX and slow inactivation of unmodified Na+ channels in which GTX was permitted to bind only to the open state of Na+ channels indicated that unbinding reactions of GTX occur only in the closed state.