Slow inactivation of Na+ current and slow cumulative spike adaptation in mouse and guinea‐pig neocortical neurones in slices.

Abstract

1. Spike adaptation of neocortical pyramidal neurones was studied with sharp electrode recordings in slices of guinea-pig parietal cortex and whole-cell patch recordings of mouse somatosensory cortex. Repetitive intracellular stimulation with 1 s depolarizing pulses delivered at intervals of <5 s caused slow, cumulative adaptation of spike firing, which was not associated with a change in resting conductance, and which persisted when Co2+ replaced Ca2P in the bathing medium.2. Development of slow cumulative adaptation was associated with a gradual decrease in maximal rates of rise of action potentials, a slowing in the post-spike depolarization towards threshold, and a positive shift in the threshold voltage for the next spike in the train; maximal spike repolarization rates and after-hyperpolarizations were unchanged.3. The data suggested that slow adaptation reflects use-dependent removal of Nae channels from the available pool by an inactivation process which is much slower than fast, Hodgkin-Huxley-type inactivation. 4. We therefore studied the properties of Na+ channels in layer II-III mouse neocortical cells using the cell-attached configuration of the patch-in-slice technique. These had a slope conductance of 18 + 1 pS and an extrapolated reversal potential of 127 + 6 mV above resting potential (Vr) (mean +S.E.M.; n = 5). Vr was estimated at -72 + 3 mV (n = 8), based on the voltage dependence of the steady-state inactivation (h,,) curve.5. Slow inactivation (SI) of Na channels had a mono-exponential onset with To between0O86 and 2-33 s (n = 3). Steady-state SI was half-maximal at -43-8 mV and had a slope of 14-4 mV (e-fold)-. Recovery from a 2 s conditioning pulse was bi-exponential and voltage dependent; the slow time constant ranged between0O45 and 2-5 s at voltages between -128 and -68 mV. 6. The experimentally determined parameters of SI were adequate to simulate slow cumulative adaptation of spike firing in a single-compartment computer model. 7. Persistent Na+ current, which was recorded in whole-cell configuration during slow voltage ramps (35 mVs-1), also underwent pronounced SI, which was apparent when the ramp was preceded by a prolonged depolarizing pulse.

Enhancement of Excitatory Synaptic Integration by GABAergic Inhibition in the Subthalamic Nucleus

“…Despite evidence that neurons possess a considerable reserve of Na v channels (Madeja, 2000), reductions in Na v channel availability during repetitive firing or pharmacological manipulation influence AP generation (Fleidervish et al, 1996;Colbert et al, 1997;Jung et al, 1997;Madeja, 2000;Colbert and Pan, 2002;Carr et al, 2003). In support of this principle, a 47% reduction in Na v channel availability in STN neurons with 5 nM TTX did not abolish pacemaking but did reduce its frequency and depolarized APth.…”

Beginning at the end: Repetitive firing properties in the final common pathway

“…Although the focus continued to be on AHP conductance summation, subsequent investigators considered other processes, particularly in studies on brainstem motoneurons, where the AHP conductance was found to contribute to the early but not later phases of SFA (Sawczuk et al, 1997;Powers et al, 1999;Viana et al, 1993). Studies in neurons of the substantia gelatinosa (Melnick et al, 2004), dorsal root ganglion cells (Blair and Bean, 2003), neocortical neurons (Fleidervish et al, 1996), and hypoglossal motoneurons (Powers et al, 1999) demonstrated that SFA was not necessarily dependent on the AHP and led to the suggestion that the slow inactivation of sodium currents may be a contributing factor.…”

Diversity of Gain Modulation by Noise in Neocortical Neurons: Regulation by the Slow Afterhyperpolarization Conductance

“…Indeed, spike-frequency adaptation introduced by an AHP conductance does not cause noise to increase gain in leaky integrate-and-fire models (Rauch et al, 2003;La Camera et al, 2004), indicating that the ability of the sAHP to promote gain increases by noise must depend on interaction with other mechanisms. In neocortical pyramidal neurons, slow inactivation of voltage-gated Na ϩ channels contributes to spike-frequency adaptation and limits the maximal steady-state firing rate during strong stimuli (Fleidervish et al, 1996). Because of its shunting effect, the sAHP conductance may increase the Na ϩ conductance required to initiate a spike, enhancing the effect of Na ϩ inactivation and limiting the maximal firing rate.…”