Mechanism of voltage-dependent gating in skeletal muscle chloride channels

• Published in: Biophysical journal Vol. 71; no. 2; pp. 695 - 706
• Main Authors: Fahlke, C., Rosenbohm, A., Mitrovic, N., George, A.L., Rüdel, R.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.1996
• Subjects: Animals; Cell Line; Chloride Channels - biosynthesis; Chloride Channels - drug effects; Chloride Channels - physiology; Chlorides - pharmacology; Cytoplasm - physiology; Egtazic Acid - pharmacology; Electric Organ - physiology; Humans; Hydrogen-Ion Concentration; Ion Channel Gating - drug effects; Kidney; Membrane Potentials - drug effects; Models, Biological; Models, Structural; Muscle Proteins - biosynthesis; Muscle Proteins - drug effects; Muscle Proteins - physiology; Muscle, Skeletal - physiology; Recombinant Proteins - biosynthesis; Recombinant Proteins - drug effects; Recombinant Proteins - metabolism; Torpedo; Transfection
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/S0006-3495(96)79269-X

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.