Density of voltage-gated potassium channels is a bifurcation parameter in pyramidal neurons

Abstract

Several types of intrinsic dynamics have been identified in brain neurons. Type 1 excitability is characterized by a continuous frequency-stimulus relationship and, thus, an arbitrarily low frequency at threshold current. Conversely, Type 2 excitability is characterized by a discontinuous frequency-stimulus relationship and a nonzero threshold frequency. In previous theoretical work we showed that the density of Kv channels is a bifurcation parameter, such that increasing the Kv channel density in a neuron model transforms Type 1 excitability into Type 2 excitability. Here we test this finding experimentally, using the dynamic clamp technique on Type 1 pyramidal cells in rat cortex. We found that increasing the density of slow Kv channels leads to a shift from Type 1 to Type 2 threshold dynamics, i.e., a distinct onset frequency, subthreshold oscillations, and reduced latency to first spike. In addition, the action potential was resculptured, with a narrower spike width and more pronounced afterhyperpolarization. All changes could be captured with a two-dimensional model. It may seem paradoxical that an increase in slow K channel density can lead to a higher threshold firing frequency; however, this can be explained in terms of bifurcation theory. In contrast to previous work, we argue that an increased outward current leads to a change in dynamics in these neurons without a rectification of the current-voltage curve. These results demonstrate that the behavior of neurons is determined by the global interactions of their dynamical elements and not necessarily simply by individual types of ion channels.

GABA regulates resonance and spike rate encoding via a universal mechanism that underlies the modulation of action potential generation

“…Changing the neuron's intrinsic conductance increases the non-zero onset AP frequency of fast spiking inter-neurons in rat somatosensory cortex (Tateno et al, 2004), and while pyramidal neurons are class-I excitable in vitro, they are class-II in vivo (Prescott et al, 2008b). Manipulating potassium conductances through cholinergic modulation of M-currents (Stiefel et al, 2008), changing the potassium channel density (Golomb et al, 1997;Zeberg et al, 2015) in pyramidal cells, or applying 4-AP to mesencephalic V neurons (Liu et al, 2008;Yang et al, 2009) are known to alter the excitability class of neurons. During neuronal development, conductance changes adjust AP latency and precision (Franzen et al, 2015).…”

“…The ordinary Bogdanov-Takens bifurcation has been characterized as an organizing center for transitions to resonance (Izhikevich, 2010;Ermentrout & Terman, 2010) and saddle-node-loop points to induce bistability (Izhikevich, 2010;Ermentrout & Terman, 2010). Potassium channel density can induce changes in excitability class as observed in simulations of fly neurons (Berger & Crook, 2015) and cortical neurons (Golomb et al, 1997;Arhem et al, 2006;Arhem & Blomberg, 2007;Zeberg et al, 2015). The BTC-structure captures these individual transitions in a single unifying framework.…”

Entropic clocks in the service of electrical signaling: ‘Ball and chain’ mechanisms for ion channel inactivation and clustering

“…Still, even with these 'chain'-level variations, the chain assumed to be extended. Furthermore, 'ball'-level regulation of the binding process by direct recognition motif phosphorylation [41], oxidation [16], protonation [64] or heme-binding [65] has been documented. Finally, regulation at the 'ball' acceptor site-level is possible, as demonstrated by RNA editing of the message for a residue found at the Kv channel inner vestibule [13].…”

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.…”