Tenidap, a novel anti-inflammatory agent, is an opener of the inwardly rectifying K+ channel hKir2.3.
We studied the effect of a novel anti-inflammatory agent, tenidap, on a cloned inwardly rectifying K+ channel, hKir2.3. Tenidap (a) potently potentiated 86Rb+ efflux through hKir2.3 channels expressed in Chinese hamster ovary cells (EC50=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; EC50=1.3 microM.), and (c) caused dose-dependent and Ba2+-sensitive membrane hyperpolarizations and concurrent decreases in input resistance. Potentiation of hKir2.3 by tenidap was unaffected by inhibitors of phospholipase A2, 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 micro1 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.
Liu
Yi
Y
Icagen, Inc., 4222 Emperor Boulevard, Suite 460, Durham, NC 27703, USA. yliu@icagen.com
Liu
Dong
D
Printzenhoff
David
D
Coghlan
Michael J
MJ
Harris
Richard
R
Krafte
Douglas S
DS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism; D016466:CHO Cells; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D000078183:Oxindoles; D015221:Potassium Channels / Q000819:agonists / Q000378:metabolism* / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007211:Indoles; C099489:KCNJ4 protein, human; D000078183:Oxindoles; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D016718:Arachidonic Acid; C062866:tenidap; D011493:Protein Kinase C