Mechanism of voltage-dependent gating in skeletal muscle chloride channels

Christoph Fahlke, Angela Rosenbohm, Nenad Mitrovic, Alfred L. George*, Reinhardt Rüdel

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Voltage-dependent gating was investigated in a recombinant human skeletal muscle Cl- channel, hCIC-1, heterologously expressed in human embryonic kidney (HEK-293) cells. Gating was found to be mediated by two qualitatively distinct processes. One gating step operates on a microsecond time scale and involves the rapid rearrangement of two identical intramembranous voltage sensors, each consisting of a single titratable residue. The second process occurs on a millisecond time scale and is due to a blocking-unblocking reaction mediated by a cytoplasmic gate that interacts with the ion pore of the channel. These results illustrate a rather simple structural basis for voltage sensing that has evolved in skeletal muscle Cl- channels and provides evidence for the existence of a cytoplasmic gating mechanism in an anion channel analogous to the 'ball and chain' mechanism of voltage-gated cation channels.

Original languageEnglish (US)
Pages (from-to)695-706
Number of pages12
JournalBiophysical Journal
Issue number2
StatePublished - Aug 1996

ASJC Scopus subject areas

  • Biophysics

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