DIFFERENTIAL MODULATION OF PANCREATIC BETA-CELL BURSTING BY INTRACELLULAR PH IN THE PRESENCE AND ABSENCE OF A K-ATP CHANNEL BLOCKER

The study of the influence of intracellular pH (pH(i)) changes on the mechanism underlying pancreatic beta-cell bursting has been hampered b y concomitant effects on the activity of background ATP-dependent K+(K -ATP) channels, beta-cells were made to burst in the absence of active K-ATP channels by raising external Ca2+ in the presence of 11 mM gluc ose and tolbutamide. An alkalinizing pH(i) shift (exposure to 20 mM NH 4Cl) increased the burst active phase duration. Conversely, an acidify ing shift (NH4Cl withdrawal) suppressed the electrical activity. This is the mirror image of the effects recorded in the absence of tolbutam ide. Glibenclamide and quinine suppressed the alkalinization-evoked hy perpolarization. This study emphasizes the differential sensitivity of different beta-cell ion channels to pH(i) and the prevalent role of K -ATP channels as electrical transducers of cytoplasmic pH changes unde r regular physiological conditions.