title: 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.
authors.affiliation: Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; and Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, United Kingdom hugo.zeberg@ki.se.
authors.forename: Hugo
authors.initials: H
authors.lastname: Zeberg
authors.affiliation: Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Hugh P C
authors.initials: HP
authors.lastname: Robinson
authors.affiliation: Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; and.
authors.forename: Peter
authors.initials: P
authors.lastname: Århem
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000465:Algorithms; D000818:Animals; D016000:Cluster Analysis; D005583:Fourier Analysis; D007700:Kinetics; D008959:Models, Neurological; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D017966:Pyramidal Cells / Q000502:physiology*; D017208:Rats, Wistar; D013003:Somatosensory Cortex / Q000502:physiology; D013696:Temperature; D046509:Tissue Culture Techniques
chemical_list: D024642:Potassium Channels, Voltage-Gated
keywords: bifurcation; dynamic clamp; ion channel density; pyramidal neuron; threshold dynamics