Channelopathies

Abstract

Channelopathies are a heterogeneous group of disorders resulting from the dysfunction of ion channels located in the membranes of all cells and many cellular organelles. These include diseases of the nervous system (e.g., generalized epilepsy with febrile seizures plus, familial hemiplegic migraine, episodic ataxia, and hyperkalemic and hypokalemic periodic paralysis), the cardiovascular system (e.g., long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia), the respiratory system (e.g., cystic fibrosis), the endocrine system (e.g., neonatal diabetes mellitus, familial hyperinsulinemic hypoglycemia, thyrotoxic hypokalemic periodic paralysis, and familial hyperaldosteronism), the urinary system (e.g., Bartter syndrome, nephrogenic diabetes insipidus, autosomal-dominant polycystic kidney disease, and hypomagnesemia with secondary hypocalcemia), and the immune system (e.g., myasthenia gravis, neuromyelitis optica, Isaac syndrome, and anti-NMDA [N-methyl-D-aspartate] receptor encephalitis). The field of channelopathies is expanding rapidly, as is the utility of molecular-genetic and electrophysiological studies. This review provides a brief overview and update of channelopathies, with a focus on recent advances in the pathophysiological mechanisms that may help clinicians better understand, diagnose, and develop treatments for these diseases.

Keywords: Channelopathies; Genetics; Ion channels; Pathophysiology.

Fig. 1

Two main types of channelopathies.

Fig. 2

Three dimensional models depicting voltage-gated sodium channels in 3 different states.

Fig. 3

Diagram showing a clinical spectrum of muscle channelopathies ranging from myotonia to flaccid paralysis.

Fig. 4

Major ionic currents that contribute to the cardiac myocyte action potential in relation to the surface electrocardiogram. I_to1, transient outward potassium current; I_Ca,L, L-type inward calcium current; I_Kr, rapid delayed-rectifier potassium current; I_Ks, slow delayed-rectifier potassium current; I_K1, inwardly-rectifying potassium current.

Fig. 5

Diagram illustrating the relationship between K_ATP channel activity and insulin secretory disorders.