Extracellular Potassium Homeostasis: Insights from Hypokalemic Periodic Paralysis

Abstract

The extracellular potassium makes up only about 2% of the total body potassium store. The majority of the body potassium is distributed in the intracellular space, and of which about 80% is in skeletal muscle. Movement of potassium in and out of skeletal muscle thus plays a pivotal role in extracellular potassium homeostasis. The exchange of potassium between the extracellular space and skeletal muscle is mediated by specific membrane transporters. These include potassium uptake by Na+, K+-ATPase and release by inward rectifier K+ channels. These processes are regulated by circulating hormones, peptides, ions, and by physical activity of muscle as well as dietary potassium intake. Pharmaceutical agents, poisons and disease conditions also affect the exchange and alter extracellular potassium concentration. Here, we review extracellular potassium homeostasis focusing on factors and conditions that influence the balance of potassium movement in skeletal muscle. Recent findings that mutations of a skeletal muscle-specific inward rectifier K+ channel cause hypokalemic periodic paralysis provide interesting insights into the role of skeletal muscle in extracellular potassium homeostasis. These recent findings will be reviewed.

Intelligent NFC potassium measurement strip with hemolysis check in capillary blood

“…The concentration of potassium in the extracellular fluid is a critical determinant of the resting membrane potential of cells and must be maintained within a narrow range, normally between 3.5 mM and 5 mM in plasma concentration [6]. The detection of anomalies in the potassium level of patients in a precarious condition is thus essential.…”

Familial Hypokalemic Periodic Paralysis with Myotonic Phenomenon : Case Report

“…Serum potassium levels are usually normal in HypoPP patients at the baseline [10]. Typically, attacks occur at night and the patient awakes paralyzed [3].…”

Phospholemman, a major regulator of skeletal muscle Na+/K+-ATPase, is not mutated in probands with hypokalemic periodic paralysis

“…It is now recognized that HypoPP is caused by aberrant potassium transport from the extracellular to the intracellular space (2). According to pedigree analysis, the inheritance pattern of the disease is autosomal dominant and several mutations in genes encoding ion channels have been identified (2)(3)(4).…”

“…It is now recognized that HypoPP is caused by aberrant potassium transport from the extracellular to the intracellular space (2). According to pedigree analysis, the inheritance pattern of the disease is autosomal dominant and several mutations in genes encoding ion channels have been identified (2)(3)(4). However, the known HypoPP-related genetic mutations do not account for all cases and electrophysiological studies (5-7) of functional changes in ion channels with such mutations have not satisfactorily explained the pathophysiological mechanism of HypoPP.…”

“…The intracellular K + content in skeletal muscles is ~46 times that in the extracellular compartment (8). Furthermore, potassium movement in and out of skeletal muscles has a crucial role in maintaining extracellular potassium homeostasis (2). Specific membrane transporters, including sodium pumps (also known as Na + /K + -ATPase) and inward-rectifier K + channels, are vital for the exchange of potassium between the extracellular and intracellular spaces in skeletal muscle (9).…”