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Effects of chloride transport on bistable behaviour of the membrane potential in mouse skeletal muscle
Author(s) -
Foppen R. J. Geukes,
Mil H. G. J.,
Heukelom J. Siegenbeek
Publication year - 2002
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2001.013298
Subject(s) - bumetanide , depolarization , hyperpolarization (physics) , chemistry , cotransporter , biophysics , membrane potential , extracellular , potassium , intracellular , chloride , sodium , biochemistry , stereochemistry , biology , organic chemistry , nuclear magnetic resonance spectroscopy
The lumbrical skeletal muscle fibres of mice exhibited electrically bistable behaviour due to the nonlinear properties of the inwardly rectifying potassium conductance. When the membrane potential ( V m ) was measured continuously using intracellular microelectrodes, either a depolarization or a hyperpolarization was observed following reduction of the extracellular potassium concentration (K + o ) from 5.7 m m to values in the range 0.76–3.8 m m , and V m showed hysteresis when K + o was slowly decreased and then increased within this range. Hypertonicity caused membrane depolarization by enhancing chloride import through the Na + –K + –2Cl − cotransporter and altered the bistable behaviour of the muscle fibres. Addition of bumetanide, a potent inhibitor of the Na + ‐K + ‐2Cl − cotransporter, and of anthracene‐9‐carboxylic acid, a blocker of chloride channels, caused membrane hyperpolarization particularly under hypertonic conditions, and also altered the bistable behaviour of the cells. Hysteresis loops shifted with hypertonicity to higher K + o values and with bumetanide to lower values. The addition of 80 μM BaCl 2 or temperature reduction from 35 to 27 °C induced a depolarization of cells that were originally hyperpolarized. In the K + o range of 5.7–22.8 m m , cells in isotonic media (289 mmol kg −1 ) responded nearly Nernstianly to K + o reduction, i.e. 50 mV per decade; in hypertonic media this dependence was reduced to 36 mV per decade (319 mmol kg −1 ) or to 31 mV per decade (340 mmol kg −1 ). Our data can explain apparent discrepancies in Δ V m found in the literature. We conclude that chloride import through the Na + –K + –2Cl − cotransporter and export through Cl − channels influenced the V m and the bistable behaviour of mammalian skeletal muscle cells. The possible implication of this bistable behaviour in hypokalaemic periodic paralysis is discussed.