Nature Neuroscience 8, 1752 - 1759 (2005)
Published online: 30 October 2005; | doi:10.1038/nn1573
BK channel  4 subunit reduces dentate gyrus excitability and protects against temporal lobe seizuresRobert Brenner1, 4, Qing H Chen1, 4, Alex Vilaythong2, Glenn M Toney1, Jeffrey L Noebels2
& Richard W Aldrich31
Department of Physiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229, USA. 2
Department of Neurology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. 3
Howard Hughes Medical Institute, Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA. 4
These authors contributed equally to this manuscript.
Correspondence should be addressed to Robert Brenner brennerr@uthscsa.edu or Richard W Aldrich raldrich@leland.stanford.edu Synaptic inhibition within the hippocampus dentate gyrus serves a 'low-pass filtering' function that protects against hyperexcitability that leads to temporal lobe seizures. Here we demonstrate that calcium-activated potassium (BK) channel accessory  4 subunits serve as key regulators of intrinsic firing properties that contribute to the low-pass filtering function of dentate granule cells. Notably, a critical 4 subunit function is to preclude BK channels from contributing to membrane repolarization and thereby broaden action potentials. Longer-duration action potentials secondarily recruit SK channels, leading to greater spike frequency adaptation and reduced firing rates. In contrast, granule cells from 4 knockout mice show a gain-of-function for BK channels that sharpens action potentials and supports higher firing rates. Consistent with breakdown of the dentate filter, 4 knockouts show distinctive seizures emanating from the temporal cortex, demonstrating a unique nonsynaptic mechanism for gate control of hippocampal synchronization leading to temporal lobe epilepsy.
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