Different fast-gate regulation by external Cl- and H+ of the muscle-type ClC chloride channels

Mei Fang Chen, Tsung-Yu Chen

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


The fast gate of the muscle-type ClC channels (ClC-0 and ClC-1) opens in response to the change of membrane potential (V). This gating process is intimately associated with the binding of external Cl- to the channel pore in a way that the occupancy of Cl- on the binding site increases the channel's open probability (Po). External H+ also enhances the fast-gate opening in these channels, prompting a hypothesis that protonation of the binding site may increase the Cl- binding affinity, and this is possibly the underlying mechanism for the H+ modulation. However, Cl- and H-, modulate the fast-gate Po-V curve in different ways. Varying the external Cl- concentrations ([Cl-]o) shifts the Po-V curve in parallel along the voltage axis, whereas reducing external pH mainly increases the minimal Po of the curve. Furthermore, H+ modulations at saturating and nonsaturating [Cl-]o are similar. Thus, the H+ effect on the fast gating appears not to be a consequence of an increase in the Cl- binding affinity. We previously found that a hyperpolarization-favored opening process is important to determine the fastgate Po of ClC-0 at very negative voltages. This [Cl-]o-independent mechanism attracted little attention, but it appears to be the opening process that is modulated by external H+.

Original languageEnglish (US)
Pages (from-to)23-32
Number of pages10
JournalJournal of General Physiology
Issue number1
StatePublished - 2001


  • Channel gating
  • Cl dependence
  • ClC-0
  • ClC-1
  • pH regulation

ASJC Scopus subject areas

  • Physiology


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