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