Cytoplasmic ATP inhibition of CLC-1 is enhanced by low pH.
The CLC-1 Cl(-) channel is abundantly expressed on the plasma membrane of muscle cells, and the membrane potential of muscle cells is largely controlled by the activity of this Cl(-) channel. Previous studies showed that low intracellular pH increases the overall open probability of recombinant CLC-1 channels in various expression systems. Low intracellular pH, however, is known to inhibit the Cl(-) conductance on the native muscle membrane, contradicting the findings from the recombinant CLC-1 channels in expressed systems. Here we show that in the presence of physiological concentrations of ATP, reduction of the intracellular pH indeed inhibits the expressed CLC-1, mostly by decreasing the open probability of the common gate of the channel.
Center foor Neuroscience and Department of Neurology, University of California, Davis, CA 95616, USA.
Pang-Yen
PY
Tseng
Brett
B
Bennetts
Tsung-Yu
TY
Chen
D000255:Adenosine Triphosphate / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D003593:Cytoplasm / Q000502:physiology; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D009132:Muscles / Q000166:cytology / Q000502:physiology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D014982:Xenopus laevis
C086321:CLC-1 channel; D018118:Chloride Channels; D000255:Adenosine Triphosphate