Identification of two types of ATP-sensitive K⁺ channels in rat ventricular myocytes

The ATP-sensitive K⁺ (K_ATP) channels are known to provide a functional linkage between the electrical activity of the cell membrane and metabolism. Two types of inwardly rectifying K⁺ channel subunits (i.e., Kir6.1 and Kir6.2) with which sulfonylurea receptors are associated were reported to constitute the K_ATP channels. In this study, we provide evidence to show two types of K_ATP channels with different biophysical properties functionally expressed in isolated rat ventricular myocytes. Using patch-clamp technique, we found that single-channel conductance for the different two types of K_ATP channels in these cells was 57 and 21 pS. The kinetic properties, including mean open time and bursting kinetics, did not differ between these two types of K_ATP channels. Diazoxide only activated the small-conductance K_ATP channel, while pinacidil and dinitrophenol stimulated both channels. Both of these K_ATP channels were sensitive to block by glibenclamide. Additionally, western blotting, immunochemistry, and RT-PCR revealed two types of Kir6.X channels, i.e., Kir6.1 and Kir6.2, in rat ventricular myocytes. Single-cell Ca²⁺ imaging also revealed that similar to dinitrophenol, diazoxide reduced the concentration of intracellular Ca²⁺. The present results suggest that these two types of K_ATP channels may functionally be related to the activity of heart cells.