Effects of chloride transport on bistable behaviour of the membrane potential in mouse skeletal muscle

J Physiol. 2002 Jul 1;542(Pt 1):181-91. doi: 10.1113/jphysiol.2001.013298.


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 mM to values in the range 0.76-3.8 mM, 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 microM BaCl2 or temperature reduction from 35 to 27 degrees C induced a depolarization of cells that were originally hyperpolarized. In the K+o range of 5.7-22.8 mM, cells in isotonic media (289 mmol x 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 x kg(-1)) or to 31 mV per decade (340 mmol x kg(-1)). Our data can explain apparent discrepancies in DeltaV(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.

MeSH terms

  • Animals
  • Barium / pharmacology
  • Bumetanide / pharmacology
  • Cell Membrane / metabolism
  • Chloride Channels / metabolism*
  • Diuretics / pharmacology
  • Electrophysiology
  • Female
  • In Vitro Techniques
  • Kinetics
  • Male
  • Membrane Potentials / physiology
  • Mice
  • Muscle, Skeletal / metabolism*
  • Osmolar Concentration
  • Patch-Clamp Techniques
  • Potassium Channel Blockers / pharmacology
  • Sodium-Potassium-Chloride Symporters / metabolism
  • Temperature


  • Chloride Channels
  • Diuretics
  • Potassium Channel Blockers
  • Sodium-Potassium-Chloride Symporters
  • Bumetanide
  • Barium