Sensitivity of volume-sensitive Cl- conductance in human epithelial cells to extracellular nucleotides

• Published in: The American journal of physiology Vol. 271; no. 6 Pt 1; p. C1872
• Main Authors: Tsumura, T, Oiki, S, Ueda, S, Okuma, M, Okada, Y
• Format: Journal Article
• Language: English
• Published: United States 01.12.1996
• Subjects: Adenosine Diphosphate - pharmacology; Adenosine Triphosphate - pharmacology; Cell Line; Chloride Channels - metabolism; Chlorides - metabolism; Cyclic AMP - pharmacology; Humans; Intestinal Mucosa - metabolism; Ion Transport - drug effects; Patch-Clamp Techniques
• ISSN: 0002-9513
• DOI: 10.1152/ajpcell.1996.271.6.c1872

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.