Physiological basis of a steady endogenous current in rat lumbrical muscle.

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Abstract
In an attempt to determine the mechanism by which rat skeletal muscle endplates generate a steady outward current, the effects of several drugs (furosemide, bumetanide, 9-anthracenecarboxylic acid [9-AC]) and changes in external ion concentration (Na+, K+, Cl-, Ba2+) on resting membrane potential(Vm) and on the steady outward current were measured. Each of the following treatments caused a 10-15 mV hyperpolarization of the membrane: replacement of extracellular Cl- with isethionate, addition of furosemide or bumetanide, and addition of 9-AC. Cl- may be actively accumulated by the muscle fibers, and the equilibrium potential of Cl- is possibly more positive than the membrane potential. Removal of external Na+ also caused a large hyperpolarization and is consistent with evidence in other tissues that active Cl- accumulation requires external Na+. The same treatments greatly reduced or abolished the steady outward current, with a time course that paralleled the changes in Vm. These results cannot be explained by a model in which the steady outward current is assumed to arise as a result of a nonuniform distribution of Na+ conductance, but they are consistent with models in which the steady current is produced by a nonuniform distribution of GCl or GK. Other treatments (Na+-free and L+-free solutions, and 50 .mu.M BaCl2) caused a temporary reversal of the steady current. Parallel measurements of Vm suggested that in none of these cases did the electrochemical driving force for K+ change sign, which makes it unlikely that the steady current arises as a result of a nonuniform distribution of GK. All the results are consistent with a model in which the steady state outward current arises as a result of a nonuniform distribution of Cl- conductance, with GCl lower near the endplate than in extrajunctional regions.