The human mitochondrial K_(ATP) channel is modulated by calcium and nitric oxide: a patch-clamp approach

摘要

ATP-sensitive potassium channels of the inner mitochondrial membrane (mtK_(ATP)) are blocked by ATP. They are suggested to be involved in protective mechanisms such as ischemic preconditioning (IPC). Here we identify this channel type for the first time in a human cell line (Jurkat cells). Vesicles of the inner mitochondrial membrane (mitoplasts) were prepared by hypoosmotic shock. Single-channel currents were measured by means of the patch-clamp technique. We identified an outward-rectifying channel with a slope conductance of 15 and 82 pS at negative and positive potentials, respectively. The block by 5-hydroxydecanoic acid and inhibition by ATP characterize this channel as the mtK_(ATP) channel. ATP also increased the frequency of events within the burst. This effect was modulated by the Ca~(2+)-bath concentration. We also show that the human mtK_(ATP) channel is a direct target for nitric oxide that blocked the channel activity. Although the molecular structure of this channel type is still unknown, its characterization as an outward-rectifying channel and modulation by calcium ions and nitric oxide may help to elucidate its functional significance, which possibly implicates a role in cell survival after IPC.