Channelopathies include diseases of the nervous system, the cardiovascular system (e.g., long QT syndrome, short QT syndrome), the respiratory system (e.g., cystic fibrosis), the endocrine system (e.g., neonatal diabetes mellitus, the urinary system (e.g. nephrogenic diabetes insipidus, autosomal-dominant polycystic kidney disease), and the immune system (e.g., myasthenia gravis).
Classifying channelopathies is difficult as a large amount of heterogeneity and phenotypic variations are observed among the various diseases. With the recent advances in deciphering the role of ion channels in the human body, the list of channelopathies is expanding. The treatment approach for the majority…
A multitude of human and animal diseases are caused by ion-channel dysfunction. This may be genetic, i.e. caused directly by mutations in genes coding for ion channels. Such diseases are called ‘channelopathies’. Examples of channelopathies are cystic fibrosis, epilepsy, and cardiac arrhythmias, e.g. the long QT syndrome. Diseases may also result from defects caused by mutations in genes coding for proteins that regulate ion channels.
The aim of this issue on Ion Channels and Disease is to briefly describe the historical development of the protein ion channel concept, the measurements used to determine how channels work at the molecular level, some consequences of their failure, and how channels (or biomimetic analogues of them) might prove useful in diagnosing and/or managing disease.
There are a number of diverse syndromes involving skeletal muscle which are associated with abnormalities in ion channels. These clinically fall into two broad groups: those with non-dystrophic myotonia or those with periodic paralysis.
Long QT syndrome, short QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia are inherited primary electrical disorders that predispose to sudden cardiac death in the absence of structural heart disease. Also known as cardiac channelopathies, primary electrical disorders respond to mutations in genes encoding cardiac ion channels and/or their regulatory proteins, which result in modifications in the cardiac action potential or in the intracellular calcium handling that lead to electrical instability and life-threatening ventricular arrhythmias.
In the gastrointestinal (GI) tract, abnormalities in secretion, absorption, motility, and sensation have been implicated in functional gastrointestinal disorders (FGIDs). Ion channels play important roles in all these GI functions.
Ion channels are involved in the physiological function and pathophysiological responses of the cardiovascular system. Atherosclerosis, hypertension, coronary artery disease, and other diseases change the expression and function of vascular ion channels, leading to vascular dysfunction and pathogenesis.
There are many diseases related to ion channels. Mutations in muscle voltage-gated sodium, potassium, calcium and chloride channels, and acetylcholine-gated channel may lead to such physiological disorders as hyper- and hypokalemic periodic paralysis, myotonias, long QT syndrome,
Disorders of ion channels (channelopathies) are increasingly being identified, making this a rapidly expanding area of neurology. Ion channel function may be controlled by changes in voltage (voltage gated), chemical interaction (ligand gated), or by mechanical perturbation.
Our heart beats as the result of an elegant interplay of ions at the cellular level. Ion channels for sodium (Na+), potassium (K+), and calcium (Ca2+) in the myocardial cellular membrane are responsible for allowing this interplay across the membrane. When genetic abnormalities cause these channels to be dysfunctional, the resulting cardiac channelopathies can predispose to life-threatening arrhythmias.
In some cases, channelopathies are passed along from parents to their children. Other times, they are the result of a genetic mutation of unknown causes.
Ion channels are transmembrane proteins specifically involved with the transport of inorganic ions like Na+, K+, Ca2+, or Cl-. Ion channels are “gated”, i.e. they open in response to a specific stimulus, such as a change in membrane potential (voltage-gated ion channels) or the binding of a neurotransmitter (ligand-gated ion channels).
In our blog “Beyond the Ion Channel”, we try to make our research more understandable, digestable and interpretable. We would like to share and discuss recent findings in epilepsy genetics on this blog, which is usually updated three times a week.