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Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110
Locke, Rachel E. and Jeanne M. Nerbonne. Role of voltage-gated K+ currents in mediating the regular-spiking phenotype of callosal-projecting rat visual cortical neurons. J. Neurophysiol. 78: 2321-2335, 1997. Whole cell current- and voltage-clamp recordings were combined to examine action potential waveforms, repetitive firing patterns, and the functional roles of voltage-gated K+ currents (IA, ID, and IK) in identified callosal-projecting (CP) neurons from postnatal (day 7-13) rat primary visual cortex. Brief (1 ms) depolarizing current injections evoke single action potentials in CP neurons with mean ± SD (n = 60) durations at 50 and 90% repolarization of 1.9 ± 0.5 and 5.5 ± 2.0 ms, respectively; action potential durations in individual cells are correlated inversely with peak outward current density. During prolonged threshold depolarizing current injections, CP neurons fire repetitively, and two distinct, noninterconverting "regular-spiking" firing patterns are evident: weakly adapting CP cells fire continuously, whereas strongly adapting CP cells cease firing during maintained depolarizing current injections. Action potential repolarization is faster and afterhyperpolarizations are more pronounced in strongly than in weakly adapting CP cells. In addition, input resistances are lower and plateau K+ current densities are higher in strongly than in weakly adapting CP cells. Functional studies reveal that blockade of ID reduces the latency to firing an action potential, and increases action potential durations at 50 and 90% repolarization. Blockade of ID also increases firing rates in weakly adapting cells and results in continuous firing of strongly adapting cells. After applications of millimolar concentrations of 4-aminopyridine to suppress IA (as well as block ID), action potential durations at 50 and 90% repolarization are further increased, and firing rates are accelerated over those observed when only ID is blocked. Using VClamp/CClamp and the voltage-clamp data in the preceding paper, mathematical descriptions of IA, ID, and IK are generated and a model of the electrophysiological properties of rat visual cortical CP neurons is developed. The model is used to simulate the firing properties of strongly adapting and weakly adapting CP cells and to explore the functional roles of IA, ID, and IK in shaping the waveforms of individual action potentials and controlling the repetitive firing properties of these cells.
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