Is there a role for potassium channel openers in neuronal ion channel disorders?
Malfunction in ion channels, due to mutations in genes encoding channel proteins or the presence of autoantibodies, are increasing being implicated in causing disease conditions, termed channelopathies. Dysfunction of potassium (K(+)) channels has been associated with the pathophysiology of a number of neurological, as well as peripheral, disorders (e.g., episodic ataxia, epilepsy, neuromyotonia, Parkinson's disease, congenital deafness, long QT syndrome). K(+) channels, which demonstrate a high degree of diversity and ubiquity, are fundamental in the control of membrane depolarisation and cell excitability. A common feature of K(+) channelopathies is a reduction or loss of membrane potential repolarisation. The identification of K(+) channel subtype specific openers will allow the recovery of the mechanism(s) responsible for counteraction of uncontrolled cellular depolarisation. Synthetic agents that demonstrate K(+) channel opening properties are available for a variety of K(+) channel subtypes (e.g., K(ATP), BK(Ca), GIRK and M-channel). This study reviews the realistic therapeutic potential that may be gained in a broad spectrum of clinical conditions by K(+) channel openers. K(+) channel openers would therefore identify dysfunctional K(+) channel as therapeutic targets for clinical benefit, in addition being able to modulate normally functioning K(+) channels to gain clinical management of pathophysiological events irrespective of the cause.
Lawson
K
K
Biomedical Research Centre, Sheffield Hallam University, School of Science and Mathematics, City Campus, Sheffield, S1 1WB, UK. K.Lawson@shu.ac.uk
D000631:Aminopyridines / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001259:Ataxia / Q000188:drug therapy / Q000235:genetics; D002219:Carbamates / Q000494:pharmacology / Q000627:therapeutic use; D003981:Diazoxide / Q000494:pharmacology / Q000627:therapeutic use; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000235:genetics; D020386:Isaacs Syndrome / Q000188:drug therapy / Q000235:genetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008818:Mice, Neurologic Mutants; D009154:Mutation; D009422:Nervous System Diseases / Q000188:drug therapy / Q000235:genetics*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics; D010655:Phenylenediamines / Q000494:pharmacology / Q000627:therapeutic use; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics*
D000631:Aminopyridines; D000927:Anticonvulsants; D000959:Antihypertensive Agents; D002219:Carbamates; D007473:Ion Channels; D018696:Neuroprotective Agents; D010655:Phenylenediamines; D015221:Potassium Channels; C101866:ezogabine; C034161:flupirtine; D003981:Diazoxide