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

Abstract

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 beta 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 beta 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.

Na+/K+ pump interacts with the h-current to control bursting activity in central pattern generator neurons of leeches

“…The Na + /K + pump is principally credited with maintaining the intracellular concentrations of Na + and K + (Ritchie, 1971; Clausen, 2005). Although the pump generates an outward current, its contribution to the resting membrane potential is often too small to be detectable (Thomas, 1972a).…”

Acute and chronic hypoxia: implications for cerebral function and exercise tolerance

“…Based on this limitation, it was, presumably falsely concluded that AH had no impact on the exercise-induced reduction in muscle maximal Na + -K + -ATPase activity. However, given the lack of isotime comparisons to date, the potential for hypoxia-related exacerbations in the maximal Na + -K + -ATPase activity as a major determinant of the hastened development of peripheral fatigue in AH should not be discarded (92). …”

3D 23Na MRI of human skeletal muscle at 7 Tesla: initial experience

“…When an action potential (leading to muscle contraction) is generated, there is a rapid, passive influx of sodium ions and efflux of potassium ions via other types of channels. During intense contractile activity, there is a persistent influx of sodium ions and efflux of potassium ions, which degrades the transmembrane Na + and K + gradients, leading to loss of membrane excitability and muscle contractility [10, 11]. Such loss of membrane excitability is believed to represent one of the main mechanisms of muscle fatigue [12].…”