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

A bstract : Skeletal muscles have a high content of Na + ‐K + ‐ATPase, an enzyme that is identical to the Na + ‐K + pump, a transport system mediating active extrusion of Na + from the cells and accumulation of K + in the cells. The major function of the Na + ‐K + pumps is to maintain the concentration gradients for Na + and K + across the plasma membrane. This generates the resting membrane potential, allowing the propagation of action potentials, excitation‐contraction coupling and force development. Muscles exposed to (1) high extracellular K + or (2) low extracellular Na + show a considerable loss of force. A similar force decline is elicited by (3) increasing Na + permeability or (4) decreasing K + permeability. Under all of these four conditions, stimulation of the Na + ‐K + pumps can restore contractility. Following exposure to electroporation or fatiguing stimulation, muscle cell membranes develop leaks to Na + and K + and a partially reversible loss of force. The restoration of force is abolished by blocking the Na + ‐K + pumps and markedly improved by stimulating the Na + ‐K + pumps with β 2 ‐agonists, calcitonin gene‐related peptide, or dbcAMP. These observations indicate that the Na + ‐K + pumps are important for the functional compensation of the commonly occurring loss of muscle cell integrity. Stimulation of the Na + ‐K + pumps with β 2 ‐agonists or other agents may be of therapeutic value in the treatment of muscle cell damage induced by electrical shocks, prolonged exercise, burns, or bruises.