Effect of Secretin and Inhibitors of HCO3-/H+ Transport on the Membrane Voltage of Rat Pancreatic Duct Cells

The aim of the present study was to study the effect of secretin on the electrophysiological response of pancreatic ducts. Furthermore, we investigated the effects of lipid-soluble buffers and inhibitors of HCO3-/H+ transport. Ducts obtained from fresh rat pancreas were perfused in vitro. Secretin depolarized the basolateral membrane voltage, Vbl, by up to 35 mV (n = 37); a half-maximal response was obtained at 3 x 10(-11) mol/l. In unstimulated ducts a decrease in the luminal Cl- concentration (120 to 37 mmol/l) had a marginal effect on Vbl, but after maximal secretin stimulation it evoked a 14 +/- 2 mV depolarization (n = 6), showing that a luminal Cl- conductance (GCl-) was activated. The depolarizing effect of secretin on Vbl was often preceded by about a 6 mV hyperpolarization, most likely due to an increase in the basolateral GK+. Perfusion of ducts with DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid, 0.01 mmol/l) or addition of ethoxzolamide (0.1 mmol/l) to the bath medium diminished the effect of secretin. Acetate or pre-treatment of ducts with NH4+/NH3 (10 mmol/l in the bath) depolarized the resting Vbl of -65 +/- 2 mV by 16 +/- 4 mV (n = 7) and 19 +/- 3 mV (n = 10), respectively. The fractional resistance of the basolateral membrane (FRbl) doubled, and the depolarizing responses to changes in bath K+ concentrations (5 to 20 mmol/l) decreased from 22 +/- 1 to 11 +/- 2 mV.(ABSTRACT TRUNCATED AT 250 WORDS)