EFFECTS OF LOWERING EXTERNAL NA-CELLS - MECHANISM OF PERIODICITY OF SPIKE-BURSTS( CONCENTRATION ON CYTOPLASMIC PH AND CA2+ CONCENTRATION INMOUSE PANCREATIC BETA)

The periodic spike-burst response of pancreatic beta-cells varies in d uration with an increase of external glucose within the range 5-20 mM. To elucidate the mechanism determining the length of spike-burst, we studied the low-Na+ induced change in electrical response to glucose w hich is similar to the change induced by high glucose. Cytoplasmic pH (pH(i)) and Ca2+ concentration ([Ca2(+)](i)) were measured by the micr ofluorometric method under normal and low-Na+ conditions in mouse panc reatic islets. Lowering external Na+ concentration from 135 to 25 mM b y replacing Na+ with Tris(+) induced progressive alkalinization in isl et cells in the presence of 11.1 mM glucose. In contrast, reduction of external Na+ by replacement with Li+ caused intracellular acidificati on. Both manipulations described above caused a marked increase in [Ca 2(+)](i), suggesting the presence of Na+/Ca2+-antiport activity. Altho ugh the change in pH(i) induced by decreasing external Na+ varied in d irection depending on the species of cations used for replacing Na+, t he pattern of electrical activity consistently changed from the spike- burst type to the continuous spike-generation type without regard for the difference in species of cations replacing Na+. These findings lea d to the following hypothesis: A decrease in Na+ influx could cause a decrease in ATP-consumption by Na+/K+-pumps that prevents the fall of intracellular ATP concentration. The resultant continuation of high co ncentrations of intracellular ATP may be responsible for the abolishme nt of the silent phase.