IS INTRACELLULAR PH AND OR INTRACELLULAR BICARBONATE A DETERMINANT OFBILE-SALT INDEPENDENT CANALICULAR BILE FORMATION - THE SUBJECT REVISITED/

Canalicular bile formation is a complex process that involves basolate ral and apical cell membrane transport, paracellular transport and ves icular transport, all of which may be subject to regulation by pH. We review the concept that epical cell membrane bicarbonate secretion pro motes bile salt independent canalicular bile formation. We show that t he presence of paracellular electrolyte transport imposes a severe res triction in interpreting data from ion substitution experiments aimed at demonstrating pH or bicarbonate dependent bile formation. Furthermo re, we report on experiments that all show stimulation of bile flow un der three disparate experimental conditions: i) intracellular alkalini zation in the absence of [HCO3-](i) or associated with a decrease of [ HCO3-](i), ii) intracellular alkalinization with an increase of [HCO3- ](i). and iii) intracellular acidification with increase of [HCO3-](i) . It is suggested that both, intracellular pH and intracellular bicarb onate may modulate canalicular bile salt independent bile formation, b ut it remains conjectural which mechanism is the prevailing one under a given experimental setting.