Читать книгу Neurology - Charles H. Clarke - Страница 90

Sodium channels open rapidly in response to depolarisation; influx of sodium underlies the upstroke of the action potential. They are structurally similar to voltage‐gated potassium channels. An important feature is that most close rapidly upon sustained depolarisation.

Impairment of such fast inactivation occurs in gain‐of‐function mutations that affect the muscle sodium channel NaV1.4 (encoded by SCN4A). Depending on severity, muscle fibres are either prone to repetitive firing (myotonia) or they enter a persistent depolarised state, with hyperkalaemia (hyperkalaemic periodic paralysis, Chapter 10).

Paradoxically, loss‐of‐function mutations of the SCN1A gene are an important cause of monogenic epilepsy. An explanation is that the α subunit of Nav1.1 is preferentially expressed in cortical interneurones. Impaired excitability of these interneurones predisposes to seizures. Other mutations of SCN1A are associated with familial hemiplegic migraine.

SCN9A, SCN10A and SCN11A encode different sodium channels expressed in peripheral nerves. Mutations that impair inactivation cause paroxysmal pain disorders. Recessive loss‐of‐function mutations can cause congenital insensitivity to pain.