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/l 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 17:1), 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 epithelia, and may represent the apical Cl- channel operating in HCl-secreting gastric parietal cells.
Sandle
G I
GI
Manchester Epithelial Membrane Research Centre, University of Manchester, UK.
Fraser
G
G
Long
S
S
Warhurst
G
G
D000230:Adenocarcinoma; D003994:Bucladesine / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology; D002463:Cell Membrane Permeability; D018118:Chloride Channels; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D004594:Electrophysiology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008565:Membrane Proteins / Q000187:drug effects / Q000502:physiology*; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000502:physiology*; D013274:Stomach Neoplasms; D014407:Tumor Cells, Cultured; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D018118:Chloride Channels; D008565:Membrane Proteins; D062367:ortho-Aminobenzoates; D005576:Colforsin; D003994:Bucladesine; D006632:Histamine; C001209:fenamic acid; D000242:Cyclic AMP