Ion channels and neurological disease: DNA based diagnosis is now possible, and ion channels may be important in common paroxysmal disorders
- Department of Clinical Neurology, Institute of Neurology, Queen Square, Lonon, UK
- Dr M G Hanna, Muscle and Neurogenetics Sections, Institute of Neurology, Queen Square, London WC1N 3BG, UK. Telephone 0171 837 3611, extension 4231; email Mhanna{at}ion.ucl.ac.uk
Ion channels are large transmembrane proteins which are essential for the normal function of all eukaryotic cells.1 They are especially important in excitable cells because they determine the membrane potential, both at rest and during firing, and also play a critical part in neurotransmitter release. Ion channels may be broadly classified into voltage gated and ligand gated, although many voltage gated channels are also affected by intracellular messengers.1 It is well recognised that autoimmune attack of the nicotinic acetylcholine receptor underlies acquired myasthenia gravis. Research over the past few years has, however, established that genetic defects in both ligand and voltage gated ion channels also cause some inherited neurological disorders.2-5Collectively, these immunological and genetic conditions have become known as the neurological channelopathies. The genetic channelopathies are listed in tables 1 and 2.
- In this window
- In a new window
Genetic voltage gated channelopathies
- In this window
- In a new window
Genetic ligand gated channelopathies
The genetic advances have increased our understanding of the molecular pathogenesis of several relatively rare muscle and CNS diseases. The immediate benefits of this are an improved classification of these disorders and the availability of DNA based diagnosis. However, an important principle has also emerged: permanent ion channel dysfunction can cause a paroxysmal neurological disturbance. By extrapolation, ion channel defects are strong candidates for other paroxysmal disorders. Some of the recently established genetic channelopathies represent rare forms of more common disorders such as migraine and epilepsy. This has led to the suggestion that the genetic susceptibility known to exist in these common disorders may be mediated through variations in ion channel function.
In this article we review some of the many recently established genetic neurological channelopathies in which DNA based diagnosis is becoming available. We do not discuss the congenital myasthenic syndromes or hyperekplexia.6 7 Also, we speculate on possible future channelopathies and discuss …
