Effect of grayanotoxin I on SA node and right atrial myocardia of the rabbit

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Abstract
Grayanotoxin I (GTX I) extracted from the leaves of Ericaceae caused both SA nodal and right atrial membranes of the rabbit to depolarize reversibly by 3.6 and 26 mV (mean values), respectively. In the presence of GTX I, either withdrawal of Na+ from the external medium or application of 10 .mu.M tetrodotoxin (TTX) reversed the depolarized membrane to the original resting potential level or hyperpolarized it beyond that level. Therefore, it is thought that GRX I specifically increases the membrane permeability to Na. The apparent dissociation constant of GTX I in depolarizing the resting membrane is estimated to be 74 .mu.M. GTX I also affected the action potential generating mechanism. The Na inactivation curve was shifted to the hyperpolarized direction by 5 mV in 25 .mu.M GTX I and by 7 mV in 50 .mu.M GTX I without changing the slope factor. There is also an evident correlation between the magnitude of GTX I-induced depolarization and the level of the maximum rate of rise of the action potential. The relative sensitivity of a preparation to GTX I may be related to Na-channel density. GTX I at a concentration up to 30 .mu.M exerted a positive inotropic action on the atrium that was counteracted by TTX at a concentration of 10 .mu.M.