EFFECT OF BICARBONATE ON POTASSIUM CONDUCTANCE OF ISOLATED PERFUSED RAT PANCREATIC DUCTS

The aim of this study was to investigate the role of the K+ conductance in unstimulated and stimulated pancreatic ducts and to see how it is affected by provision of exogenous HCO3-/CO2. For this purpose we have applied electrophysiological techniques to perfused pancreatic ducts, which were dissected from rat pancreas. The basolateral membrane potential PD(bl) of unstimulated duct cells was between -60 mV and -70 mV, and the cells had a relatively large K+ conductance in the basolateral membrane as demonstrated by (a) 20-22 mV depolarization of PD(bl) in response to increase in bath K+ concentration from 5 mmol/l to 20 mmol/l and (b) the effect of a K+ channel blocker, Ba2+ (5 mmol/l), which depolarized PD(bl) by 30-40 mV. These effects on unstimulated ducts were relatively independent of bath HCO3-/CO2. The luminal membrane seemed to have no significant K+ conductance. Upon stimulation with secretin or dibutyryl cyclic AMP. PD(bl) depolarized to about -35 mV in the presence of HCO3-/CO2. Notably, the K+ conductance in the stimulated ducts was now only apparent in the presence of exogenous HCO3-/CO2 in the bath solutions. Upon addition of Ba2+, PD(bl) depolarized by 13 +/- 1 mV (n = 7), the fractional resistance of the basolateral membrane, FR(bl) increased from 0.66 to 0.78 (n = 6), the specific transepithelial resistance, R(te), increased from 52 +/- 13-OMEGA-cm2 to 59 +/- 15-OMEGA-cm2 (n = 11), and the whole-cell input resistance, R(c), measured with double-barrelled electrodes, increased from 20 M-OMEGA to 26 M-OMEGA (n = 3). These results are consistent with Ba2+ inhibition of the K+ conductance. Following removal of exogenous HCO3-/CO2 in the same ducts, stimulation led to a larger depolarization on PD(bl) to about -25 mV, and Ba2+ had a smaller effect on PD(bl) and no significant effect on the resistances. The individual resistances in the duct epithelium were estimated from equivalent circuit analysis. The luminal membrane resistance, R(l), decreased from about 2000-OMEGA-cm2 to 80-OMEGA-cm2 upon stimulation. The basolateral membrane resistance, R(bl), remained at 90-120-OMEGA-cm2 and the paracellular shunt resistance, R(s), at 50-80-OMEGA-cm2. Ba2+ increased R(bl) Of stimulated ducts to about 200-OMEGA-cm2 an effect present only if the ducts were provided with exogenous HCO3-/CO2. Taken together, the present results indicate that the basolateral K+ conductance of pancreatic ducts is sensitive to exogenous HCO3-/CO2, i.e. without HCO3-/CO2 the conductance becomes very low although the ducts are undergoing stimulation.