SUPPRESSING NA-CELLS( INFLUX INDUCES AN INCREASE IN INTRACELLULAR ATPCONCENTRATION IN MOUSE PANCREATIC BETA)

The effects of suppressing Na+ influx on the activity of ATP-sensitive K+ channels (K(ATP) channel) and intracellular ATP concentration in m ouse pancreatic beta-cells were studied. Lowering extracellular Na+ co ncentration brought about a closing of K(ATP) channels. The activity o f K(ATP) channels was markedly inhibited by the addition of amiloride, a blocker of Na+/H+-counter transporter. Mannoheptulose completely el iminated the inhibition otherwise induced by amiloride. Monensin, an e lectroneutral Na+/H+ antiporter, remarkably increased the activity of K(ATP) channels. Removing extracellular Ca2+ also caused inhibition of the channel activity. ATP measurement experiments using isolated isle ts revealed that the intracellular ATP concentration of islet cells wa s significantly increased by incubating either with amiloride or a low Na+ solution. The measurement of fluorescence excited at 360 nm demon strated that both suppressing Na+ influx and inhibition of Na+/K+-pump s caused a transient increase in the reduced form of pyridine nucleoti de. These findings indicate that a decrease in Na+ influx could cause an elevation in intracellular ATP concentration probably through induc ing a fall in ATP consumption at the Na+/K+-pump sites.