Mechanism of voltage-dependent gating in skeletal muscle chloride channels

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

doi:10.1016/S0006-3495(96)79269-X

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

Pharmacology

Research output: Contribution to journal › Article › peer-review

66 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	695-706
Number of pages	12
Journal	Biophysical Journal
Volume	71
Issue number	2
DOIs	https://doi.org/10.1016/S0006-3495(96)79269-X
State	Published - Aug 1996

Funding

Supported by the DFG (Ru 138/17-3 and Fa 301/1-1), the Muscular Dystrophy Association, and the Lucille P. Markey Charitable Trust. ALG is a Lucille P. Markey Scholar.

ASJC Scopus subject areas

Biophysics

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10.1016/S0006-3495(96)79269-X

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title = "Mechanism of voltage-dependent gating in skeletal muscle chloride channels",

abstract = "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.",

author = "Christoph Fahlke and Angela Rosenbohm and Nenad Mitrovic and George, {Alfred L.} and Reinhardt R{\"u}del",

note = "Funding Information: Supported by the DFG (Ru 138/17-3 and Fa 301/1-1), the Muscular Dystrophy Association, and the Lucille P. Markey Charitable Trust. ALG is a Lucille P. Markey Scholar.",

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AU - Rosenbohm, Angela

AU - Mitrovic, Nenad

AU - George, Alfred L.

AU - Rüdel, Reinhardt

N1 - Funding Information: Supported by the DFG (Ru 138/17-3 and Fa 301/1-1), the Muscular Dystrophy Association, and the Lucille P. Markey Charitable Trust. ALG is a Lucille P. Markey Scholar.

PY - 1996/8

Y1 - 1996/8

N2 - 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.

AB - 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.

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Mechanism of voltage-dependent gating in skeletal muscle chloride channels

Abstract

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