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 Ca 2+ -independent depolarization-activated K + currents in callosalprojecting rat visual cortical neurons. J. Neurophysiol. 78: 2309Neurophysiol. 78: -2320Neurophysiol. 78: , 1997. Whole cell, Ca 2+ -independent, depolarization-activated K + currents were characterized in identified callosalprojecting (CP) neurons isolated from postnatal day 7-16 rat primary visual cortex. CP neurons were identified in vitro after in vivo retrograde labeling with fluorescently tagged latex microbeads. During brief (160-ms) depolarizing voltage steps to potentials between −50 and +60 mV, outward K + currents in these cells activate rapidly and inactivate to varying degrees. Three distinct K + currents were separated based on differential sensitivity to 4-aminopyridine (4-AP); these are referred to here as I A , I D , and I K , because their properties are similar (but not identical) K + currents termed I A , I D , and I K in other cells. The current sensitive to high (≥ 100 μM) concentrations of 4-AP (I A ) activates and inactivates rapidly; the current blocked completely by low (≤ 50 μM) 4-AP (I D ) activates rapidly and inactivates slowly. A slowly activating, slowly inactivating current (I K ) remains in the presence of 5 mM 4-AP. I A , I D , and I K also were separated and characterized in experiments that did not rely on the use of 4-AP. All CP cells express all three K + current types, although the relative densities of I A , I D , and I K vary among cells. The experiments here also have revealed that I A , I D , and I K display similar voltage dependences of activation and steady state inactivation, whereas the kinetic properties of the currents are distinct. At + 30 mV, for example, mean ± SD activation τs are 0.83 ± 0.24 ms for I A , 1.74 ± 0.49 ms for I D , and 14.7 ± 4.0 ms for I K . Mean ± SD inactivation τs for I A and I D are 26 ± 7 ms and 569 ± 143 ms, respectively. Inactivation of I K is biexponential with mean ± SD inactivation time constants of 475 ± 232 ms and 3,128 ± 1,328 ms; ∼20% of the 4-AP-insensitive current is noninactivating. For all three components, activation is voltage dependent, increasing with increasing depolarization, whereas inactivation is voltage independent. Both I A and I K recover rapidly from steady state inactivation with mean ± SD recovery time constants of 38 ± 7 ms and 79 ± 26 ms, respectively; I D recovers an order of magnitude more slowly (588 ± 274 ms). The properties of I A , I D , and I K in CP neurons are compared with those of similar currents described previously in other mammalian central neurons and, in the accompanying paper, the roles of these conductances in regulating the firing properties of CP neurons are explored.

The synaptic activity transmitted from vestibular hair cells of the lagena to primary afferent neurons was recorded in vitro using sharp, intracellular microelectrodes. At rest, the activity was composed of miniature excitatory postsynaptic potentials (mEPSPs) at frequencies from 5 to 20/s and action potentials (APs) at frequencies betwen 0 and 10/s. mEPSPs recorded from a single fiber displayed a large variability. For mEPSPs not triggering APs, amplitudes exhibited an average coefficient of variance (CV) of 0.323 and rise times an average CV of 0.516. APs were only triggered by mEPSPs with larger amplitudes (estimated 4-6 mV) and/or steeper maximum rate of rise (10.9 mV/ms, +/- 3.7 SD, n=4 experiments) compared to (3.50 mV/ms, +/-0.07 SD, n=6 experiments) for nontriggering mEPSPs. The smallest mEPSPs showed a fast rise time (0.99 ms between 10% and 90% of peak amplitude) and limited variability across fibers (CV:0.18) confirming that they were not attenuated signals, but rather represented single-transmitter discharges (TDs). The mEPSP amplitude and rise-time relationship suggests that many mEPSPs represented several, rather than a single pulse of secretion of TDs. According to the estimated overall TD frequency, the coincidence of TDs contributing to the same mEPSP were not statistically independent, indicating a positive interaction between TDs that is reminiscent of the way subminiature signals group to form miniature signals at the neuromuscular junction. Depending on the duration and intensity of efferent stimulation, a complete block of AP initiation occurred either immediately or after a delay of a few seconds. Efferent stimulation did not significantly change AP threshold level, but abruptly decreased mEPSP frequency to a near-complete block that followed the block of APs. Maximum mEPSP rate of rise decreased during, and recovered progressively after, efferent stimulation. After termination of efferent stimulation, mEPSP amplitude did not recover instantly and for a few seconds the amplitude distribution of synaptic events showed fewer large-amplitude events than during the control period. This confirms that mEPSP amplitude and rate of rise properties, which are critical for triggering afferent APs, are modified by efferent activity. The depression of afferent AP firing during efferent stimulation corresponded to a decrease in mEPSP frequency and, to a lesser extent, a decrease in mEPSP amplitude and rate of rise, suggesting, a decrease in the level of interaction among TDs contibuting to a mEPSP.

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