Role of Voltage-Gated K⁺ Currents in Mediating the Regular-Spiking Phenotype of Callosal-Projecting Rat Visual Cortical Neurons

Abstract

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.

Three Kinetically Distinct Ca2+-Independent Depolarization-Activated K+ Currents in Callosal-Projecting Rat Visual Cortical Neurons

“…Because neurons that retract their callosal projections during postnatal development do not die or undergo changes in morphology or transmitter phenotype (Olavarria and Van Sluyters 1985; J. M. Nerbonne and A. Burkhalter, unpublished observations), both the cells that retain and the cells that retract their callosal projections were expected to display regular-spiking behavior. As demonstrated in the subsequent paper (Locke and Nerbonne 1997), current-clamp recordings have revealed that this hypothesis is correct, i.e., all of the cells labeled in early postnatal animals based on the callosal projection are regular-spiking cortical neurons.…”

“…Here, we show that there are three kinetically and pharmacologically distinct Ca 2+ -independent, voltagegated K + currents expressed in CP cells that we refer to as I A , I D , and I K because their properties are similar (although not identical) to I A , I D , and I K currents described in other mammalian central neurons. In the companion paper (Locke and Nerbonne 1997), we demonstrate that CP neurons are indeed regular spiking, and we explore the roles of I A , I D , and I K in shaping the waveforms of action potentials and in regulating the firing properties of CP neurons.…”

Postnatal development of A-type and Kv1- and Kv2-mediated potassium channel currents in neocortical pyramidal neurons

“…The greatest changes occur between weeks 1 and 3 Lorenzon and Foehring 1993;Locke and Nerbonne 1997a;Maravall et al 2004b;Metherate and Aramakis 1999). Both Kv1 (Guan et al 2006b)-and Kv2 (Foehring et al 2009)-mediated currents regulate interspike intervals in these cells.…”

Functional Role of the Fast Transient Outward K+CurrentIAin Pyramidal Neurons in (Rat) Primary Visual Cortex

“…Combined action potential and voltage-clamp recordings, for example, suggest that I A channels likely play an important role in action potential repolarization in cortical pyramidal neurons (Kang et al, 2000). It has also been demonstrated that the input resistances of visual cortical neurons are increased in the presence of an often used I A -selective blocker, 4-aminopyridine (4-AP) (Locke and Nerbonne, 1997b). In addition, the current thresholds for action potential generation and the latency to firing are reduced, and action potentials are reportedly prolonged significantly ( p Ͻ 0.001) in the presence of millimolar concentrations of 4-AP (Locke and Nerbonne, 1997b).…”

“…It has also been demonstrated that the input resistances of visual cortical neurons are increased in the presence of an often used I A -selective blocker, 4-aminopyridine (4-AP) (Locke and Nerbonne, 1997b). In addition, the current thresholds for action potential generation and the latency to firing are reduced, and action potentials are reportedly prolonged significantly ( p Ͻ 0.001) in the presence of millimolar concentrations of 4-AP (Locke and Nerbonne, 1997b). In visual cortical neurons, however, I D is also blocked effectively by millimolar 4-AP (Locke and Nerbonne, 1997a).…”