title: Membrane excitability, weakness, and fatigue.
abstract: A failure in membrane excitability, defined as an inability of the sarcolemma and T-tubule to translate the neural discharge command into repetitive action potentials, represents an inviting cause of mechanical disfunction in both health and disease. A failure at this level would precipitate a disturbance in signal transmission between the T-tubule and the calcium release channels of the sarcoplasmic reticulum, resulting in reduced release of Ca2+, lower cytosolic free Ca2+ levels, and depressed myofibrillar activation and force generation. The ability of the sarcolemma and T-tubules to conduct repetitive action potentials is intimately dependent on active transport of Na+ and K+ following an action potential. The active transport of these cations is mediated by the Na+-K+-ATPase, an integral membrane protein that uses the energy from the hydrolysis of 1 ATP to transport 3 Na+ out of the cell and 2 K+ into the cell. A failure to recruit sufficient Na+-K+-ATPase activity during contractile activity could result in a rundown of the transmembrane gradients for Na+ and K+, leading to a loss of membrane excitability. The Na+-K+-ATPase activity depends on the amount and isoform composition of the protein, substrate availability, and acute regulatory factors. Each of these factors is examined as a potential cause of altered activation of the Na+-K+-ATPase activity and loss of membrane excitability in fatigue. Regular exercise represents a potent stimulus for upregulating Na+-K+-ATPase levels and for increasing the ability for cation transport across the sarcolemma and T-tubule membrane. As such, training may be a valuable tool in the management of fatigue in health and disease.
authors.affiliation: Department of Kinesiology, University of Waterloo, Waterloo, Ontario.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Green
mesh_terms: D002462:Cell Membrane / Q000502:physiology*; D006801:Humans; D008564:Membrane Potentials; D009119:Muscle Contraction / Q000502:physiology; D018763:Muscle Fatigue / Q000502:physiology*; D018908:Muscle Weakness / Q000503:physiopathology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology
chemical_list: D000254:Sodium-Potassium-Exchanging ATPase