Tenidap, a novel anti-inflammatory agent, is an opener of the inwardly rectifying K+ channel hKir2.3.

Abstract We studied the effect of a novel anti-inflammatory agent, tenidap, on a cloned inwardly rectifying K + channel, hKir2.3. Tenidap (a) potently potentiated 86 Rb + efflux through hKir2.3 channels expressed in Chinese hamster ovary cells (EC 50 =402 nM), (b) reversibly and dose-dependently increased whole-cell and macro-patch hKir2.3 currents (maximum whole-cell current response to tenidap was 230±27% of control; EC 50 =1.3 μM.), and (c) caused dose-dependent and Ba 2+ -sensitive membrane hyperpolarizations and concurrent decreases in input resistance. Potentiation of hKir2.3 by tenidap was unaffected by inhibitors of phospholipase A 2 , protein kinase C, or arachidonic acid metabolic pathways. The action of tenidap was not intracellular. Tenidap also had little or no effect on currents flowing through hKir2.1, Kv1.5, and μ1 Na + channels. Our results demonstrate that tenidap is a potent opener of hKir2.3 and suggest that it can serve as a valuable pharmacological tool for studying physiological and pathological processes involving Kir2.3.