Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2005-11-24
pubmed:abstractText
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 beta4 subunits serve as key regulators of intrinsic firing properties that contribute to the low-pass filtering function of dentate granule cells. Notably, a critical beta4 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 beta4 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, beta4 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1097-6256
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1752-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16261134-Action Potentials, pubmed-meshheading:16261134-Adaptation, Physiological, pubmed-meshheading:16261134-Animals, pubmed-meshheading:16261134-Cell Communication, pubmed-meshheading:16261134-Cell Membrane, pubmed-meshheading:16261134-Dentate Gyrus, pubmed-meshheading:16261134-Disease Models, Animal, pubmed-meshheading:16261134-Epilepsy, Temporal Lobe, pubmed-meshheading:16261134-Female, pubmed-meshheading:16261134-Genetic Predisposition to Disease, pubmed-meshheading:16261134-Ion Channel Gating, pubmed-meshheading:16261134-Large-Conductance Calcium-Activated Potassium Channels, pubmed-meshheading:16261134-Male, pubmed-meshheading:16261134-Mice, pubmed-meshheading:16261134-Mice, Inbred C57BL, pubmed-meshheading:16261134-Mice, Knockout, pubmed-meshheading:16261134-Neural Inhibition, pubmed-meshheading:16261134-Neural Pathways, pubmed-meshheading:16261134-Organ Culture Techniques, pubmed-meshheading:16261134-Protein Subunits, pubmed-meshheading:16261134-Small-Conductance Calcium-Activated Potassium Channels, pubmed-meshheading:16261134-Synaptic Transmission
pubmed:year
2005
pubmed:articleTitle
BK channel beta4 subunit reduces dentate gyrus excitability and protects against temporal lobe seizures.
pubmed:affiliation
Department of Physiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural