ATP-sensitive potassium channel: A novel target for protection against UV-induced human skin cell damage

Ultraviolet radiation (UV) induces cell damages leading to skin photoaging and skin cancer. ATP‐sensitive potassium (KATP) channel openers (KCOs) have been shown to exert significant myocardial preservation and neuroprotection in vitro and in vivo, and yet the potential role of those KCOs in protection against UV‐induced skin cell damage is unknown. We investigated the effects of pinacidil and diazoxide, two classical KCOs, on UV‐induced cell death using cultured human keratinocytes (HaCat cells). Here, we demonstrated for the first time that Kir 6.1, Kir 6.2 and SUR2 subunits of KATP channels are functionally expressed in HaCaT cells and both non‐selective KATP channel opener pinacidil and mitoKATP (mitochondrial KATP) channel opener diazoxide attenuated UV‐induced keratinocytes cell death. The protective effects were abolished by both non‐selective KATP channel blocker glibenclamide and selective mitoKATP channel blocker 5‐hydroxydecanoate (5‐HD). Also, activation of KATP channel with pinacidil or diazoxide resulted in suppressive effects on UV‐induced MAPK activation and reactive oxygen species (ROS) production. Unexpectedly, we found that the level of intracellular ROS was slightly elevated in HaCaT cells when treated with pinacidil or diazoxide alone. Furthermore, UV‐induced mitochondrial membrane potential loss, cytochrome c release and ultimately apoptotic cell death were also inhibited by preconditioning with pinacidil and diazoxide, and their effects were reversed by glibenclamide and 5‐HD. Taken together, we contend that mitoKATP is likely to contribute the protection against UV‐induced keratinocytes cell damage. Our findings suggest that KATP openers such as pinacidil and diazoxide may be utilized to prevent from UV‐induced skin aging. J. Cell. Physiol. 212: 252–263, 2007. © 2007 Wiley‐Liss, Inc.