Key result
In the presence of physiological concentrations of ATP, reduction of intracellular pH inhibits the expressed CLC-1 channel by decreasing the open probability of its common gate.
This study resolves a contradiction between native and recombinant CLC-1 channels by demonstrating that physiological ATP is required for low intracellular pH to inhibit the channel's open probability.
Resolves native-recombinant CLC-1 discrepancies; leaves open in vivo relevance for muscle excitability.
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.
No takes yet. Share an insight, caveat, or question.
Tseng et al. (2007) studied this question. Low intracellular pH with physiological ATP was evaluated on CLC-1 channel open probability. In the presence of physiological concentrations of ATP, reduction of intracellular pH inhibits the expressed CLC-1 channel by decreasing the open probability of its common gate.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: