A POSSIBLE ROLE OF THE ATP-SENSITIVE POTASSIUM-ION CHANNEL IN DETERMINING THE DURATION OF SPIKE-BURSTS IN MOUSE PANCREATIC BETA-CELLS

The pancreatic beta-cell displays an electrical activity consisting of spike bursts and silent phases at glucose concentrations of about 10 mM. The mechanism of initial depolarization induced by glucose is well defined. However, the mechanism inducing the silent phase has not bee n fully elucidated. In the present study, the possibility of involveme nt of ATP-sensitive K+ channels in repolarization was examined using t he patch-clamp technique in the cell-attached recording configuration. Ouabain (0.1 mM), an inhibitor of Na+/K+-ATPase, caused a complete: s uppression of ATP-sensitive K+ channel activity followed by typical bi phasic current deflections, which were due to action potentials. The c hannel activity was also inhibited by removal of K+ from a perifusion solution. Furthermore, the activity of ATP-sensitive K+ channels was m arkedly inhibited either by replacement of external NaCl with LiCl or by addition of amiloride (0.2 mM), a blocker of Na+/H+ antiport. Addit ion of L-type Ca2+ channel blockers such as Nifedipine or Mn2+ induced the complete suppression of K+ channel activity, These findings stron gly suggest that a fall in ATP consumption results in sustained depola rization, and that the repolarizations interposed between spike-bursts under normal ionic conditions are due to the periodical fall of ATP c oncentration brought about by periodical acceleration of ATP consumpti on at Na+/K+-pumps. It is concluded that the elevation of intracellula r Na+ concentration as a consequence of accelerated Na+/Ca2+-countertr ansport during the period of spike-burst enhances ATP consumption, lea ding to a fall in ATP concentration which is responsible for terminati on of spike-burst and initiation of repolarization.