INHIBITION OF CA2-DEPENDENT CL- CHANNELS FROM SECRETORY EPITHELIAL-CELLS BY LOW INTERNAL PH()

The actions of intracellular pH (pH(i)> on Ca2+-dependent Cl- channels were studied in secretory epithelial cells derived from human colon c arcinoma (T84) and in isolated rat parotid acinar cells. Channel curre nts were measured with the whole cell voltage clamp technique with pip ette solutions of different pH. Ca2+-dependent Cl- channels were activ ated by superfusing ionomycin to increase the intracellular calcium co ncentration ([Ca2+](i)) or by using pipette solutions with buffered Ca 2+ levels. Large currents were activated in T84 and parotid cells by b oth methods with pH(i) levels of 7.3 or 8.3. Little or no Cl- channel current was activated with pH(i) at 6.4. We used on-cell patch clamp m ethods to investigate the actions of low pH(i) on single Cl- channel c urrent amplitude in T84 cells. Lowering the pH(i) had little or no eff ect on the current amplitude of a 8 pS Cl- channel, but did reduce cha nnel activity. These results suggest that cytosolic acidification may be able to modulate stimulus-secretion coupling in fluid-secreting epi thelia by inhibiting the activation of Ca2+-activated Cl- channels.