Abbreviated action potential kinetics in a mouse model of potassium channel overexpression during hippocampal development.
Loss or "gain" of function mutations in voltage-gated ion channels often results in an adverse neurological phenotype. We have examined the electrical characteristics of hippocampal pyramidal cells in a transgenic mouse model to determine how overexpression of a Shaker-type potassium channel subunit during early postnatal development might alter excitability properties of developing neurons. We found that in CA3 neurons potassium channel overexpression led to a transient shortening in duration of single action potentials during the first two postnatal weeks. There was an increase in maximal repolarization rate, without significant effect on the rate of rise. Transgenic CA3 neurons also showed a decrease of firing frequency in response to sustained depolarizing current injection. In contrast, repolarization of action potentials in CA1 neurons was not significantly altered by trangene expression. Western Blot Analysis of membrane-associated transgene protein indicated that transgene protein levels decreased during development, in agreement with functional measures of spike width. Our data indicate that the functional consequences of potassium channel transgene expression are dependent on cellular environment and developmental stage. A transient period of hypoexcitability during a critical period of development for CA3 neurons may contribute to the hyperexcitable phenotype observed in adult animals.
Williams
Stephen H
SH
Department of Pharmacology, George Washington University, Washington, District of Columbia 20037, USA.
Sutherland
Margaret L
ML
D000200:Action Potentials / Q000235:genetics*; D000367:Age Factors; D000818:Animals; D001048:Aplysia / Q000235:genetics; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D004558:Electric Stimulation; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D023421:Models, Animal; D018408:Patch-Clamp Techniques; D010641:Phenotype; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism; D051637:Shaker Superfamily of Potassium Channels; D009435:Synaptic Transmission / Q000235:genetics; D013997:Time Factors; D019076:Transgenes / Q000235:genetics
D015221:Potassium Channels; D021122:Protein Subunits; D051637:Shaker Superfamily of Potassium Channels