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Are big potassium-type Ca(2+)-activated potassium channels a viable target for the treatment of epilepsy?

Leo, A; Citraro, R; Constanti, A; De Sarro, G; Russo, E; (2015) Are big potassium-type Ca(2+)-activated potassium channels a viable target for the treatment of epilepsy? Expert Opinion on Therapeutic Targets , 19 (7) pp. 911-926. 10.1517/14728222.2015.1026258. Green open access

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Abstract

INTRODUCTION: BK (big potassium) channels are Ca(2+)-activated K(+) channels widely expressed in mammalian cells. They are extensively distributed in the CNS, the most abundant level being found in brain areas largely involved in epilepsy, namely cortex, hippocampus, piriform cortex, and other limbic structures. BK channels control action potential shape/duration, thereby regulating membrane excitability and Ca(2+) signaling. AREAS COVERED: The potassium channel superfamily represents a rich source of potential targets for therapeutic intervention in epilepsy. Some studies have identified alterations in BK channel function, therefore, supporting the development of drugs acting on these channels for epilepsy treatment. EXPERT OPINION: The actual sketch is intriguing and controversial, since mechanisms altering the physiological role of BK channels leading to either a loss- or gain-of-function have both been linked to seizure onset. Not many studies have been performed to unravel the efficacy of drugs acting on these channels as potential antiepileptics; however, paradoxically, efficacy has been demonstrated for both BK channel openers and blockers. Furthermore, their potential usefulness in preventing epileptogenesis has not been investigated at all. Substantial data on risks and benefits of modulating these channels are urgently needed to draw a definitive conclusion on whether BK channels are a viable future target for the treatment of epilepsy.

Type: Article
Title: Are big potassium-type Ca(2+)-activated potassium channels a viable target for the treatment of epilepsy?
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1517/14728222.2015.1026258
Publisher version: http://dx.doi.org/10.1517/14728222.2015.1026258
Language: English
Additional information: This is an Accepted Manuscript of an article published by Taylor & Francis in Expert Opinion on Therapeutic Targets on 03/04/2015, available online: http://dx.doi.org/10.1517/14728222.2015.1026258.
Keywords: Antiepileptic drug, big potassium channel modulators, big potassium channels, epilepsy, seizures, Animals, Anticonvulsants, Brain, Calcium, Calcium Signaling, Epilepsy, Humans, Large-Conductance Calcium-Activated Potassium Channels, Molecular Targeted Therapy
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/1476407
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