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 (Ki) 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 (Ki 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.
Department of Pharmacology, University of Cambridge, U.K.
J M
JM
Treherne
M L
ML
Ashford
D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004351:Drug Resistance; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D012964:Sodium; D011188:Potassium