[HTML][HTML] Na+-K+ pump regulation and skeletal muscle contractility

T Clausen - Physiological reviews, 2003 - journals.physiology.org
T Clausen
Physiological reviews, 2003journals.physiology.org
Abstract Clausen, Torben. Na+-K+ Pump Regulation and Skeletal Muscle Contractility.
Physiol Rev 83: 1269-1324, 2003; 10.1152/physrev. 00011.2003.—In skeletal muscle,
excitation may cause loss of K+, increased extracellular K+([K+] o), intracellular Na+([Na+] i),
and depolarization. Since these events interfere with excitability, the processes of excitation
can be self-limiting. During work, therefore, the impending loss of excitability has to be
counterbalanced by prompt restoration of Na+-K+ gradients. Since this is the major function …
Abstract
Clausen, Torben. Na+-K+ Pump Regulation and Skeletal Muscle Contractility. Physiol Rev 83: 1269-1324, 2003; 10.1152/physrev. 00011.2003.—In skeletal muscle, excitation may cause loss of K+, increased extracellular K+([K+] o), intracellular Na+([Na+] i), and depolarization. Since these events interfere with excitability, the processes of excitation can be self-limiting. During work, therefore, the impending loss of excitability has to be counterbalanced by prompt restoration of Na+-K+ gradients. Since this is the major function of the Na+-K+ pumps, it is crucial that their activity and capacity are adequate. This is achieved in two ways: 1) by acute activation of the Na+-K+ pumps and 2) by long-term regulation of Na+-K+ pump content or capacity. 1) Depending on frequency of stimulation, excitation may activate up to all of the Na+-K+ pumps available within 10 s, causing up to 22-fold increase in Na+ efflux. Activation of the Na+-K+ pumps by hormones is slower and less pronounced. When muscles are inhibited by high [K+] o or low [Na+] o, acute hormone-or excitation-induced activation of the Na+-K+ pumps can restore excitability and contractile force in 10-20 min. Conversely, inhibition of the Na+-K+ pumps by ouabain leads to progressive loss of contractility and endurance. 2) Na+-K+ pump content is upregulated by training, thyroid hormones, insulin, glucocorticoids, and K+ overload. Downregulation is seen during immobilization, K+ deficiency, hypoxia, heart failure, hypothyroidism, starvation, diabetes, alcoholism, myotonic dystrophy, and McArdle disease. Reduced Na+-K+ pump content leads to loss of contractility and endurance, possibly contributing to the fatigue associated with several of these conditions. Increasing excitation-induced Na+ influx by augmenting the open-time or the content of Na+ channels reduces contractile endurance. Excitability and contractility depend on the ratio between passive Na+-K+ leaks and Na+-K+ pump activity, the passive leaks often playing a dominant role. The Na+-K+ pump is a central target for regulation of Na+-K+ distribution and excitability, essential for second-to-second ongoing maintenance of excitability during work.
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