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- W2155674018 abstract "U-54494A [(+-)-cis-3,4-dichloro-N-methyl-N-[2-(1- pyrrolidinyl)-cyclohexyl]-benzamide], an anticonvulsant and Na channel blocker, was examined for its interaction with delayed rectifier K channels in mouse neuroblastoma cells (NIE-115) using whole-cell and inside-out configurations of the patch clamp techniques. U-54494A at anticonvulsant doses reversibly blocked the tetraethylammonium-sensitive outward K current in a time-dependent manner without affecting the current-voltage relationship. Analysis of the time-dependent block suggests interaction of U-54494A with the open state, but not with the resting state of the K channel. Furthermore, the drug showed no interaction with inactivated states of the K channel because it produced no noticeable effect on the steady-state inactivation curve or the recovery of the channel activity from inactivated states. The drug shifted the steady-state activation curve to a hyperpolarizing direction. This shift seems to result from underestimations of the maximal conductance of the K channel in the presence of U-54494A, because of its progressively increasing potency to block the K currents as the membrane potential became more depolarized. The potency of the drug was enhanced not only by depolarized membrane potentials, but also by raising the external pH. These results suggest that U-54494A interacts with a channel binding site which is located within the membrane electric field and approachable from the cytoplasmic side. The proposal was supported further by single channel recordings with inside-out patches in which U-54494A induced flickery blocks of single channel openings of the delayed rectifier.(ABSTRACT TRUNCATED AT 250 WORDS)" @default.
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- W2155674018 date "1992-10-01" @default.
- W2155674018 modified "2023-09-25" @default.
- W2155674018 title "Block of voltage-gated potassium currents by anticonvulsant U-54494A in mouse neuroblastoma cells." @default.
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