Periodic paralysis

Abstract

The periodic paralyses are a group of skeletal muscle channelopathies characterizeed by intermittent attacks of muscle weakness often associated with altered serum potassium levels. The underlying genetic defects include mutations in genes encoding the skeletal muscle calcium channel Ca1.1, sodium channel Na1.4, and potassium channels K2.1, K3.4, and possibly K2.6. Our increasing knowledge of how mutant channels affect muscle excitability has resulted in better understanding of many clinical phenomena which have been known for decades and sheds light on some of the factors that trigger attacks. Insights into the pathophysiology are also leading to new therapeutic approaches.

Skeletal Muscle Channelopathies

“…Attacks are typically brought on by triggers which include diet or rest after exercise and are often associated with changes in extracellular potassium. Later in the disease course, many patients will develop fixed proximal weakness [79,[81][82][83][84][85]. Attack frequency and severity can be reduced with carbonic anhydrase inhibitors.…”

Transient thyrotoxicosis‐aggravated attacks of paralysis in a patient with hereditary hypokalemic periodic paralysis type 2

“…In patients with SCN4A mutations, the two outmost arginine residues in domain II of Nav1.4 cause a leak current, which only manifests at hyperpolarized resting membrane potentials, is very small, and lead to a minor shift of resting muscle membrane potential. 1,8 However, it has a marked In conclusion, we reported a patient with hereditary HypoPP type 2 in whom repeated thyroid function tests revealed that transient thyrotoxicosis aggravated his attacks.…”

“…Once a potential trigger effects, extracellular potassium levels are reduced in patients with HypoPP. In patients with SCN4A mutations, the two outmost arginine residues in domain II of Nav1.4 cause a leak current, which only manifests at hyperpolarized resting membrane potentials, is very small, and lead to a minor shift of resting muscle membrane potential . However, it has a marked effect on the muscle membrane during hypokalemia by increasing the potassium concentration, at which point paradoxical depolarization occurs.…”

“…However, it has a marked effect on the muscle membrane during hypokalemia by increasing the potassium concentration, at which point paradoxical depolarization occurs. At extremely low potassium levels, the majority of fibers partially depolarize . Activated 3Na + /2K + ATPase pumps could be involved in worsening hypokalemia and increasing the percentage of fibers undergoing paradoxical depolarization.…”

“…The substitution is located in the second gating charge in domain II of Nav1.4 effect on the muscle membrane during hypokalemia by increasing the potassium concentration, at which point paradoxical depolarization occurs. At extremely low potassium levels, the majority of fibers partially depolarize 1,8. Activated 3Na + /2K + ATPase pumps could be involved in worsening hypokalemia and increasing the percentage of fibers undergoing paradoxical depolarization.In TPP patients, excess triiodothyronine, increased activity of 3Na + /2K + ATPase pumps, and/or insulin can exert additional alterations to sodium channel behavior during thyrotoxicosis 6.…”