Kv4 potassium channel subunits control action potential repolarization and frequency-dependent broadening in rat hippocampal CA1 pyramidal neurones.
A-type potassium channels regulate neuronal firing frequency and the back-propagation of action potentials (APs) into dendrites of hippocampal CA1 pyramidal neurones. Recent molecular cloning studies have found several families of voltage-gated K(+) channel genes expressed in the mammalian brain. At present, information regarding the relationship between the protein products of these genes and the various neuronal functions performed by voltage-gated K(+) channels is lacking. Here we used a combination of molecular, electrophysiological and imaging techniques to show that one such gene, Kv4.2, controls AP half-width, frequency-dependent AP broadening and dendritic action potential propagation. Using a modified Sindbis virus, we expressed either the enhanced green fluorescence protein (EGFP)-tagged Kv4.2 or an EGFP-tagged dominant negative mutant of Kv4.2 (Kv4.2g(W362F)) in CA1 pyramidal neurones of organotypic slice cultures. Neurones expressing Kv4.2g(W362F) displayed broader action potentials with an increase in frequency-dependent AP broadening during a train compared with control neurones. In addition, Ca(2)(+) imaging of Kv4.2g(W362F) expressing dendrites revealed enhanced AP back-propagation compared to control neurones. Conversely, neurones expressing an increased A-type current through overexpression of Kv4.2 displayed narrower APs with less frequency dependent broadening and decreased dendritic propagation. These results point to Kv4.2 as the major contributor to the A-current in hippocampal CA1 neurones and suggest a prominent role for Kv4.2 in regulating AP shape and dendritic signalling. As Ca(2)(+) influx occurs primarily during AP repolarization, Kv4.2 activity can regulate cellular processes involving Ca(2)(+)-dependent second messenger cascades such as gene expression and synaptic plasticity.
Kim
Jinhyun
J
Molecular Neurophysiology and Biophysics Unit, Laboratory of Synaptic and Cellular Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-3715, USA.
Wei
Dong-Sheng
DS
Hoffman
Dax A
DA
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D021122:Protein Subunits; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051672:Shal Potassium Channels / Q000502:physiology*
D021122:Protein Subunits; D051672:Shal Potassium Channels