Altered ionic permeability in skeletal muscle from horses with hyperkalemic periodic paralysis

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Abstract
A recently described disorder in certain registered Quarter horses bears many clinical similarities to the muscle disease identified as hyperkalemic periodic paralysis (HPP) in humans. Pathological changes in membrane permeability or Na(+)-K+ pump activity have been proposed to produce the muscle depolarization and inexcitability that characterize the condition in humans. Biopsies of external intercostal muscle from normal and affected horses were used to determine whether alterations in either permeability and/or pump activity could be linked to the pathology in horses. Affected horse muscle is approximately 16 mV more depolarized than normal muscle at rest, and the muscle membrane potential of HPP horses is less responsive to changes in extracellular K+. Calculation of the relative membrane permeabilities of Na+ and K+ (PNa/PK) indicates that this ratio is significantly increased in HPP muscle. The increase is probably due to an increase in PNa rather than to a decrease in PK, since addition of 10(-6) M tetrodotoxin produces an approximately 14-mV membrane hyperpolarization in HPP fibers but is without effect in normal fibers. The clinical similarities between HPP in horses and humans suggest a common genetic defect in the two species.