Sensitivity of volume-sensitive Cl- conductance in human epithelial cells to extracellular nucleotides.
The sensitivity to extracellular nucleotides of volume-sensitive Cl- channel activity was investigated by whole cell and single-channel patch-clamp recordings in a human small intestinal epithelial cell line (Intestine 407) during steady osmotic swelling. Adenine nucleotides added to the bathing solution suppressed whole cell volume-sensitive Cl- currents with the potency sequence of ATP > ADP > AMP. In contrast, extracellular adenosine 3',5'-cyclic monophosphate (cAMP) at over 0.1 mM increased volume-sensitive Cl- currents in the entire voltage range examined, whereas guanosine 3',5'-cyclic monophosphate was without effect. Neither the single-channel conductance nor the open probability was affected by extracellular cAMP. Extracellular ATP (at over 30 microM), in the Mg(2+)-free form, inhibited the whole cell volume-sensitive Cl- current, preferentially in the outward direction. By exposure to extracellular ATP, the single Cl- channel current became flickery at positive potentials. These results indicate that the volume-sensitive Cl- channel in the human epithelial cell is stimulated voltage independently by extracellular cAMP but blocked voltage dependently by the Mg(2+)-free form of extracellular ATP.
Tsumura
T
T
Department of Cellular and Molecular Physiology, National Institute for Physiological Sciences, Okazaki, Japan.
Oiki
S
S
Ueda
S
S
Okuma
M
M
Okada
Y
Y
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D002460:Cell Line; D018118:Chloride Channels / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects; D018408:Patch-Clamp Techniques
D018118:Chloride Channels; D002712:Chlorides; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000242:Cyclic AMP