Ion Channel Density Regulates Switches between Regular and Fast Spiking in Soma but Not in Axons

Abstract

The threshold firing frequency of a neuron is a characterizing feature of its dynamical behaviour, in turn determining its role in the oscillatory activity of the brain. Two main types of dynamics have been identified in brain neurons. Type 1 dynamics (regular spiking) shows a continuous relationship between frequency and stimulation current (f-Istim) and, thus, an arbitrarily low frequency at threshold current; Type 2 (fast spiking) shows a discontinuous f-Istim relationship and a minimum threshold frequency. In a previous study of a hippocampal neuron model, we demonstrated that its dynamics could be of both Type 1 and Type 2, depending on ion channel density. In the present study we analyse the effect of varying channel density on threshold firing frequency on two well-studied axon membranes, namely the frog myelinated axon and the squid giant axon. Moreover, we analyse the hippocampal neuron model in more detail. The models are all based on voltage-clamp studies, thus comprising experimentally measurable parameters. The choice of analysing effects of channel density modifications is due to their physiological and pharmacological relevance. We show, using bifurcation analysis, that both axon models display exclusively Type 2 dynamics, independently of ion channel density. Nevertheless, both models have a region in the channel-density plane characterized by an N-shaped steady-state current-voltage relationship (a prerequisite for Type 1 dynamics and associated with this type of dynamics in the hippocampal model). In summary, our results suggest that the hippocampal soma and the two axon membranes represent two distinct kinds of membranes; membranes with a channel-density dependent switching between Type 1 and 2 dynamics, and membranes with a channel-density independent dynamics. The difference between the two membrane types suggests functional differences, compatible with a more flexible role of the soma membrane than that of the axon membrane.

Extracellular Linkers Completely Transplant the Voltage Dependence from Kv1.2 Ion Channels to Kv2.1

“…Given the diversity of voltage-gated ion channels (143 channel genes in the human genome (1)), it is of general interest to consider what constitutes the variability and what functional role it plays in forming and regulating neuronal firing patterns (2)(3)(4)(5)(6)(7)(8)(9)(10). The basic functional channel parameters are ion selectivity and gating, the latter characterized by opening/closing kinetics and the voltage dependence of the channel's open probability.…”

The Effect of Cell Size and Channel Density on Neuronal Information Encoding and Energy Efficiency

“…Changes in size will also affect the densities of voltage-gated ion channels altering the amount of channel noise, the spike threshold, and the maximum attainable spike rate. 9, 10, 11 These two factors, capacitance and channel density, will interact to influence the way in which the membrane filters synaptic or sensory inputs and, therefore, the information-processing capabilities of neurons. For instance, assuming the specific capacitance and the input resistance as constant, a larger passive cell would have a lower bandwidth in comparison to its smaller counterpart.…”

Bridging the Molecular-Cellular Gap in Understanding Ion Channel Clustering

“…Such changes in ionic current densities are reflected by changes in the membrane permeability to Na + and K + ions when all channels are open. In the native channel context, such modulation of ion channel densities may be brought about by specific channel blockers that serve to reduce the nominal number of active channels per site (Zeberg et al, 2010). These later studies directly demonstrate how changes in ionic current densities may affect AP conduction properties and information coding.…”

“…It has long been thought that different combinations of ion channel types may explain the observed differences in firing patterns (Prescott et al, 2008). In recent years, however, theoretical and experimental evidence has been accumulated to show that changes in the densities of voltage-gated Na + and K + channels alone can explain the dynamic switch of a neuron between the low and highfrequency firing modes (Århem et al, 2006;Århem and Blomberg, 2007;Zeberg et al, 2010;Zeberg et al, 2015). Such changes in ionic current densities are reflected by changes in the membrane permeability to Na + and K + ions when all channels are open.…”