The effects of ryanodine, 9,21-didehydroryanodine and 9,21-didehydroryanodol on two types of K+ channel (a maxi, Ca2+-activated, 170 pS channel (BK channel) and an inward rectifier, stretch-sensitive channel of 35 pS conductance (IK channel) found in the plasma membrane of locust skeletal muscle have been investigated. 10−9M-10−5M ryanodine irreversibly induced a dose-dependent reduction of the reversal potential (Vrev) of the currents of both channels, i.e. from ~60 mV in the absence of the alkaloid to ~15 mV for 10−5M ryanodine, measured under physiologically normal K+ and Na+ gradients. In both cases the change in the ionic selectivity was Ca2+-independent. 9,21-didehydroryanodine and 9,21-didehyroryanodol also reduced Vrev, but only to ~35 mV during application of 10−5M of these compounds. Additionally, 9,21-didehydroryanodine reversibly diminished the conductances of the two K+ channels. To test the hypothesis that ryanoids increase Na+ permeability by enlarging the K+ channels, the channels were probed with quaternary ammonium ions during ryanoid application. When applied to the cytoplasmic face of inside-out patches exised from locust muscle membrane, TEA blocked the K+ channels in a voltage-dependent fashion. The dissociation constant (Kd(0)) for TEA block of the IK channel was reduced from 44 mM to 1 mM by 10−7 M ryanodine, but the voltage-dependence of the block was unaffected. Qualitatively similar data were obtained for the BK channel. Ryanodine had no effect on the Kd for cytoplasmically-applied TMA. However, the voltage-dependence for TMA block was increased for both K+ channels, from 0.47 to ~0.8 with 10−6M ryanodine. The effects of ryanodine on TEA and TMA block support the hypothesis that ryanodine enlarges the K+ channels so as to facilitate permeation of partially hydrated Na+ ions.

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