Hyperkalemic periodic paralysis (HYPP, HyperKPP) is an inherited autosomal dominant disorder that affects sodium channels in muscle cells and the ability to regulate potassium levels in the blood.
Factors that can trigger attacks include rest after exercise, potassium-rich foods, stress, fatigue, weather changes, certain pollutants (e.g., cigarette smoke) and fasting.
In contrast to HyperKPP, hypokalemic periodic paralysis (noted in humans) refers to loss-of-function mutations in channels that prevent muscle depolarisation and therefore are aggravated by low potassium ion concentrations.
To prevent the muscle from being perpetually contracted, the channel contains a fast inactivation gate that plugs the sodium pore very quickly after it opens.
Mutations have been found on the cytoplasmic loops between the S4 and S5 helices of domains II, III and IV, which are the binding sites of the inactivation gate.
[4][5] The pathological mechanism of SCN4A mutations in hyperkalemic periodic paralysis is complex, but explains the autosomal dominant and hyperkalemia-related aspects of the disease.