Mechanism of voltage-dependent gating in skeletal muscle chloride channels.
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.
Fahlke
C
C
Department of General Physiology, University of Ulm, Germany.
Rosenbohm
A
A
Mitrovic
N
N
George
A L
AL
Rüdel
R
R
D000818:Animals; D002460:Cell Line; D018118:Chloride Channels / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D002712:Chlorides / Q000494:pharmacology; D003593:Cytoplasm / Q000502:physiology; D004533:Egtazic Acid / Q000494:pharmacology; D004557:Electric Organ / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000187:drug effects; D007668:Kidney; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D008961:Models, Structural; D009124:Muscle Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D014101:Torpedo; D014162:Transfection
C086321:CLC-1 channel; D018118:Chloride Channels; D002712:Chlorides; D009124:Muscle Proteins; D011994:Recombinant Proteins; D004533:Egtazic Acid