The role of chloride transport in the control of the membrane potential in skeletal muscle--theory and experiment.
We present a model for the control of the transmembrane potential of mammalian skeletal muscle cell. The model involves active and passive transport of Na(+), K(+), and Cl(-). As we check the model against experimental measurements on murine skeletal muscle cells, we find that the model can account for the observed bistability of the transmembrane potential at low extracellular potassium concentration. The effect of bumetanide, a blocker of the Na,K,2Cl-cotransporter, is measured and modeled. A hyperosmotic medium is known to stimulate the Na,K,2Cl-cotransporter and we also measure and model the effects of such a medium. Increased chloride transport has two effects on the interval along the extracellular potassium concentration axis where the system is bistable: the interval is shifted towards higher potassium concentrations and the length of the interval is reduced. Finally, we also obtain estimates for the chloride permeability (P(Cl)=2x10(-5) cm/s), for the transmembrane chemical potential of chloride, and for the steady state flux through the Na,K,2Cl-cotransporter (2x10(-11) mol/cm(2) s for chloride).
Dept. of Physics, East Carolina University, Greenville, NC 27858, USA.
Jill
J
Gallaher
Martin
M
Bier
Jan
J
Siegenbeek van Heukelom
D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D017136:Ion Transport; D008564:Membrane Potentials; D051379:Mice; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*
D002712:Chlorides; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide; D012964:Sodium; D011188:Potassium