A cAMP-activated chloride channel in the plasma membrane of cultured human gastric cells (HGT-1)

Hydrochloric acid (HCl) secretion by gastric parietal cells involves an apical Cl^– conductance, the properties of which have not been defined. In the present study, forskolin and histamine [agonists that increase intracellular cyclic adenosine monophosphate (cAMP)], and dibutyryl cAMP, activated channels in previously quiescent cell-attached membrane patches on cultured human gastric cells (HGT-1). In the cell-attached configuration (Cl^–149 mmol/ 1 in bath and pipette), channels exhibited outward rectification, voltage dependence, inward current (–0.7 pA) at zero holding potential and a reversal potential of +24 mV, consistent with the presence of a Cl^– conductive pathway. In excised inside-out patches, channels (i) exhibited degrees of outward rectification and voltage dependence that were comparable to those seen in cell-attached patches, (ii) demonstrated a –21 mV shift of their reversal potential when bath Cl^– was decreased from 149 mmol/l to 53 mmol/l (calculated Cl^–:cation permeability ratio 171), and (iii) were highly sensitive to the Cl^– channel blocker diphenylamine-2-carboxylic acid (DPC, 10^–3 mol/l). This cAMP-activated Cl^– channel bears many similarities to other Cl^– channels within intestinal epithalia, and may represent the apical Cl^– channel operating in HCl-secreting gastric parietal cells.