Extracellular cations modulate the ATP sensitivity of ATP-K$^{+}$ channels in rat ventromedial hypothalamic neurons

ATP-sensitive K$^{+}$ (ATP-K$^{+}$) channels underlie the glucose-sensing nature of pancreatic $\beta $-cells by way of their inhibition by intracellular ATP. Recently it has been proposed that ATP-K$^{+}$ channels have a similar function in certain hypothalamic neurons that become excitable in raised concentrations of extracellular glucose. The aim of this study was to assess the ATP sensitivity of ATP-K$^{+}$ channels in inside-out membrane patches excised from glucose-sensing neurons that were acutely isolated from the ventromedial nucleus of rat hypothalamus. ATP-K$^{+}$ channels were less sensitive to ATP in neurons than in other tissues. Moreover, the sensitivity of neuronal ATP-K$^{+}$ channels to inhibition by intracellular ATP was modulated by extracellular cations. Under physiological ionic gradients (i.e. high extracellular Na$^{+}$ and low K$^{+}$), intracellular ATP produced a concentration-dependent inhibition of channel activity, with a half-maximal inhibition (K$_{\text{i}}$) of 2.32 mM. A non-hydrolysable analogue of ATP, AMP(PNP), was similarly effective. In symmetrical K$^{+}$ (i.e. no extracellular sodium), channel activity was tenfold more sensitive to ATP (K$_{\text{i}}$ of 0.21 mM). A parallel study on ATP-K$^{+}$ channels from an insulin-secreting $\beta $-cell line (CRI-G1) showed that, in contrast to the neuronal data, extracellular cations had no effect on the ATP sensitivity of the channel.