Na+-K+ Pump Stimulation Improves Contractility in Damaged Muscle Fibers

doi:10.1196/annals.1363.021

Skeletal muscles have a high content of Na⁺-K⁺-ATPase, an enzymethat is identical to the Na⁺-K⁺ pump, a transport system mediatingactive extrusion of Na⁺ from the cells and accumulation of K⁺in the cells. The major function of the Na⁺-K⁺ pumps is to maintainthe concentration gradients for Na⁺ and K⁺ across the plasmamembrane. This generates the resting membrane potential, allowingthe propagation of action potentials, excitation-contractioncoupling and force development. Muscles exposed to (1) highextracellular K⁺ or (2) low extracellular Na⁺ show a considerableloss of force. A similar force decline is elicited by (3) increasingNa⁺ permeability or (4) decreasing K⁺ permeability. Under allof these four conditions, stimulation of the Na⁺-K⁺ pumps canrestore contractility. Following exposure to electroporationor fatiguing stimulation, muscle cell membranes develop leaksto Na⁺ and K⁺ and a partially reversible loss of force. Therestoration of force is abolished by blocking the Na⁺-K⁺ pumpsand markedly improved by stimulating the Na⁺-K⁺ pumps with ß₂-agonists,calcitonin gene-related peptide, or dbcAMP. These observationsindicate that the Na⁺-K⁺ pumps are important for the functionalcompensation of the commonly occurring loss of muscle cell integrity.Stimulation of the Na⁺-K⁺ pumps with ß₂-agonists orother agents may be of therapeutic value in the treatment ofmuscle cell damage induced by electrical shocks, prolonged exercise,burns, or bruises.