ATP inhibition of CLC-1 is controlled by oxidation and reduction.
The effect of intracellular adenosine triphosphate (ATP) on the "common gating" of the CLC-1 chloride channel has been studied by several laboratories with controversial results. Our previous study on the channel expressed in Xenopus oocytes using excised inside-out patch-clamp methods showed a robust effect of ATP in shifting the open probability curve of the common gate toward more depolarizing voltages (Tseng, P.Y., B. Bennetts, and T.Y. Chen. 2007. J. Gen. Physiol. 130:217-221). The results were consistent with those from studying the channel expressed in mammalian cells using whole cell recording methods (Bennetts, B., M.W. Parker, and B.A. Cromer. 2007. J. Biol. Chem. 282:32780-32791). However, a recent study using excised-patch recording methods for channels expressed in Xenopus oocytes reported that ATP had no direct effect on CLC-1 (Zifarelli, G., and M. Pusch. 2008. J. Gen. Physiol. 131:109-116). Here, we report that oxidation of CLC-1 may be the culprit underlying the controversy. When patches were excised from mammalian cells, the sensitivity to ATP was lost quickly--within 2-3 min. This loss of ATP sensitivity could be prevented or reversed by reducing agents. On the other hand, CLC-1 expressed in Xenopus oocytes lost the ATP sensitivity when patches were treated with oxidizing reagents. These results suggest a novel view in muscle physiology that the mechanisms controlling muscle fatigability may include the oxidation of CLC-1.
Zhang
Xiao-Dong
XD
Center for Neuroscience and Department of Neurology, University of California, Davis, Davis, CA 95618, USA.
Tseng
Pang-Yen
PY
Chen
Tsung-Yu
TY
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002461:Cell Line, Transformed; D018118:Chloride Channels / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology; D008623:Mercaptoethanol / Q000494:pharmacology; D008698:Mesylates / Q000494:pharmacology; D010084:Oxidation-Reduction; D018408:Patch-Clamp Techniques; D010618:Phenanthrolines / Q000494:pharmacology; D019163:Reducing Agents / Q000494:pharmacology*; D014981:Xenopus
C086321:CLC-1 channel; D018118:Chloride Channels; D008698:Mesylates; D010618:Phenanthrolines; D019163:Reducing Agents; C109153:(2-sulfonatoethyl)methanethiosulfonate; D008623:Mercaptoethanol; D000255:Adenosine Triphosphate; C025205:1,10-phenanthroline