Properties of volume-sensitive Cl- channels in a human epithelial cell line.
A regulatory volume decrease is accomplished by parallel activation of Ca(2+)-dependent K+ channels and Ca(2+)-independent Cl- channels in cultured human intestinal epithelial cells (Intestine 407). The anion selectivity of whole-cell currents recorded in osmotically swollen cells falls into the Eisenman type I sequence corresponding to a low-field anion channel. The volume-sensitive Cl- channel has an intermediate unitary conductance. Both the whole-cell and single-channel Cl- currents exhibit unique voltage-dependency. The Cl- current can be maintained in the activated state in the physiological voltage range. However, at very large depolarizations (over +50 mV), the current is quickly inactivated. The Cl- current shows moderate outward rectification. The whole-cell Cl- current is sensitive to Cl- channel blockers such as SITS and NPPB as well as to cis unsaturated fatty acids such as arachidonic acid and oleic acid. The whole-cell current is totally independent of Ca2+ and cyclic AMP, but inhibited by increases in cytosolic free Mg2+ ions. Removal of intracellular ATP, but not Mg2+, abolishes the Cl- current. The ATP role can be substituted for non-hydrolyzable ATP analogs. Therefore, it is likely that intracellular ATP maintains the channel activity through non-hydrolytic binding.
Okada
Y
Y
Department of Cellular and Molecular Physiology, National Institute for Physiological Sciences, Okazaki, Japan.
Kubo
M
M
Oiki
S
S
Petersen
C C
CC
Tominaga
M
M
Hazama
A
A
Morishima
S
S
D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D018118:Chloride Channels / Q000502:physiology*; D000242:Cyclic AMP / Q000494:pharmacology; D004848:Epithelium / Q000502:physiology*; D006801:Humans; D008274:Magnesium / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels; D014882:Water-Electrolyte Balance
D018118:Chloride Channels; D015221:Potassium Channels; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D008274:Magnesium; D002118:Calcium