A seizure-induced gain-of-function in BK channels is associated with elevated firing activity in neocortical pyramidal neurons.
A heritable gain-of-function in BK channel activity has been associated with spontaneous seizures in both rodents and humans. We find that chemoconvulsant-induced seizures induce a gain-of-function in BK channel current that is associated with abnormal, elevated network excitability. Action potential half-width, evoked firing rate, and spontaneous network activity in vitro were all altered 24 h following picrotoxin-induced seizures in layer 2/3 pyramidal cells in the neocortex of young mice (P13-P16). Action potential half-width and firing output could be normalized to control values by application of BK channel antagonists in vitro. Thus, both inherited and acquired BK channel gain-of-functions are linked to abnormal excitability. Because BK channel antagonists can reduce elevated firing activity in neocortical neurons, BK channels might serve as a new target for anticonvulsant therapy.
Shruti
Sonal
S
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh PA 15213, USA; Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh PA 15213, USA.
Clem
Roger L
RL
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh PA 15213, USA; Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh PA 15213, USA.
Barth
Alison L
AL
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh PA 15213, USA; Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh PA 15213, USA. Electronic address: barth@cmu.edu.
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D007211:Indoles / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000187:drug effects / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D012640:Seizures / Q000378:metabolism* / Q000503:physiopathology*
D007211:Indoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; C048220:paxilline