Lessons Learned from Muscle Fatigue: Implications for Treatment of Patients with Hyperkalemic Periodic Paralysis

Jean-Marc      Renaud; Lawrence      J. Hayward

Abstract

Hyperkalemic periodic paralysis (HyperKPP) is a disease characterized by periods of myotonic discharges and paralytic attacks causing weakness, the latter associated with increases in plasma [K+]. The myotonic discharge is due to increased Na+ influx through defective Na+ channels that triggers generation of several action potentials. The subsequent increase in extracellular K+ concentration causes excessive membrane depolarization that inactivates Na+ channels triggering the paralysis. None of the available treatments is fully effective. This paper reviews the capacity of Na+ K+ ATPase pumps, KATP and ClC-1 Cl- channels in improving membrane excitability during muscle activity and how using these three membrane components we can study future and more effective treatments for HyperKPP patients. The review of current patents related to HyperKPP reinforces the need of novel approaches for the treatment of this channelopathy.

Keywords: Skeletal muscle, muscle fatigue, muscle paralysis, hyperkalemic periodic paralysis, patients, humans, treatments, pain, muscle soreness, muscle spasms, muscle weakness, potassium, plasma potassium levels, Na+/K+ ATPase pumps, patents