Selective control of cortical axonal spikes by a slowly inactivating K+ current

Neurons are flexible electrophysiological entities in which the distribution and properties of ionic channels control their behaviors. Through simultaneous somatic and axonal whole-cell recording of layer 5 pyramidal cells, we demonstrate a remarkable differential expression of slowly inactivating K+ currents. Depolarizing the axon, but not the soma, rapidly activated a low-threshold, slowly inactivating, outward current that was potently blocked by low doses of 4-aminopyridine, α-dendrotoxin, and rTityustoxin-Kα. Block of this slowly inactivating current caused a large increase in spike duration in the axon but only a small increase in the soma and could result in distal axons generating repetitive discharge in response to local current injection. Importantly, this current was also responsible for slow changes in the axonal spike duration that are observed after somatic membrane potential change. These data indicate that low-threshold, slowly inactivating K+ currents, containing Kv1.2 α subunits, play a key role in the flexible properties of intracortical axons and may contribute significantly to intracortical processing.

[1]  Johan F. Storm,et al.  Temporal integration by a slowly inactivating K+ current in hippocampal neurons , 1988, Nature.

[2]  J. Storm Potassium currents in hippocampal pyramidal cells. , 1990, Progress in brain research.

[3]  E. Neher Correction for liquid junction potentials in patch clamp experiments. , 1992, Methods in enzymology.

[4]  M. Barish,et al.  Two pharmacologically and kinetically distinct transient potassium currents in cultured embryonic mouse hippocampal neurons , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  D. Surmeier,et al.  Voltage-gated potassium currents in acutely dissociated rat cortical neurons. , 1993, Journal of neurophysiology.

[6]  Yuh Nung Jan,et al.  Presynaptic A-current based on heteromultimeric K+ channels detected in vivo , 1993, Nature.

[7]  G A Gutman,et al.  Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. , 1994, Molecular pharmacology.

[8]  P. Schwartzkroin,et al.  Localization of Kv1.1 and Kv1.2, two K channel proteins, to synaptic terminals, somata, and dendrites in the mouse brain , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[9]  C. McBain,et al.  Potassium conductances underlying repolarization and after‐hyperpolarization in rat CA1 hippocampal interneurones. , 1995, The Journal of physiology.

[10]  J. Trimmer,et al.  Association and colocalization of K+ channel alpha- and beta-subunit polypeptides in rat brain , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  B. Robertson,et al.  Novel effects of dendrotoxin homologues on subtypes of mammalian Kv1 potassium channels expressed in Xenopus oocytes , 1996, FEBS letters.

[12]  D. Debanne,et al.  Somatic voltage‐gated potassium currents of rat hippocampal pyramidal cells in organotypic slice cultures. , 1996, The Journal of physiology.

[13]  W. Chen,et al.  Different mechanisms underlying the repolarization of narrow and wide action potentials in pyramidal cells and interneurons of cat motor cortex , 1996, Neuroscience.

[14]  F. Zhou,et al.  Layer I neurons of rat neocortex. I. Action potential and repetitive firing properties. , 1996, Journal of neurophysiology.

[15]  B. Sakmann,et al.  Action potential initiation and propagation in rat neocortical pyramidal neurons , 1997, The Journal of physiology.

[16]  B. Robertson,et al.  Patch-Clamp Recordings from Cerebellar Basket Cell Bodies and Their Presynaptic Terminals Reveal an Asymmetric Distribution of Voltage-Gated Potassium Channels , 1998, The Journal of Neuroscience.

[17]  W. F. Hopkins Toxin and subunit specificity of blocking affinity of three peptide toxins for heteromultimeric, voltage-gated potassium channels expressed in Xenopus oocytes. , 1998, The Journal of pharmacology and experimental therapeutics.

[18]  R. Miles,et al.  Cell‐attached measurements of the firing threshold of rat hippocampal neurones , 1999, The Journal of physiology.

[19]  B. Rudy,et al.  Molecular Diversity of K+ Channels , 1999, Annals of the New York Academy of Sciences.

[20]  P. Saggau,et al.  Modulation of transmitter release by action potential duration at the hippocampal CA3-CA1 synapse. , 1999, Journal of neurophysiology.

[21]  J. Dolly,et al.  alpha subunit compositions of Kv1.1-containing K+ channel subtypes fractionated from rat brain using dendrotoxins. , 1999, European journal of biochemistry.

[22]  B. Robertson,et al.  Electrophysiological Characterization of Voltage-Gated K+ Currents in Cerebellar Basket and Purkinje Cells: Kv1 and Kv3 Channel Subfamilies Are Present in Basket Cell Nerve Terminals , 2000, The Journal of Neuroscience.

[23]  P. Jonas,et al.  Dynamic Control of Presynaptic Ca2+ Inflow by Fast-Inactivating K+ Channels in Hippocampal Mossy Fiber Boutons , 2000, Neuron.

[24]  M. Saraste,et al.  FEBS Lett , 2000 .

[25]  E. Lambe,et al.  The Role of Kv1.2-Containing Potassium Channels in Serotonin-Induced Glutamate Release from Thalamocortical Terminals in Rat Frontal Cortex , 2001, The Journal of Neuroscience.

[26]  John M. Bekkers,et al.  Modulation of Excitability by α-Dendrotoxin-Sensitive Potassium Channels in Neocortical Pyramidal Neurons , 2001, The Journal of Neuroscience.

[27]  D. Wilkin,et al.  Neuron , 2001, Brain Research.

[28]  Bernardo Rudy,et al.  Kv3 channels: voltage-gated K+ channels designed for high-frequency repetitive firing , 2001, Trends in Neurosciences.

[29]  K. Rhodes,et al.  Experimental Localization of Kv1 Family Voltage-Gated K+ Channel α and β Subunits in Rat Hippocampal Formation , 2001, The Journal of Neuroscience.

[30]  M. Komada,et al.  βIV-spectrin regulates sodium channel clustering through ankyrin-G at axon initial segments and nodes of Ranvier , 2002, The Journal of cell biology.

[31]  D. Ruan,et al.  Effect of 4-aminopyridine on synaptic transmission in rat hippocampal slices , 2004, Brain Research.

[32]  D. Debanne Information processing in the axon , 2004, Nature Reviews Neuroscience.

[33]  R. Douglas,et al.  A Quantitative Map of the Circuit of Cat Primary Visual Cortex , 2004, The Journal of Neuroscience.

[34]  I. Forsythe,et al.  Presynaptic K+ channels: electrifying regulators of synaptic terminal excitability , 2004, Trends in Neurosciences.

[35]  B. Robertson,et al.  Dendrotoxins: structure-activity relationships and effects on potassium ion channels. , 2004, Current medicinal chemistry.

[36]  K. Rhodes,et al.  Localization of voltage-gated ion channels in mammalian brain. , 2004, Annual review of physiology.

[37]  Gautam B. Awatramani,et al.  Modulation of Transmitter Release by Presynaptic Resting Potential and Background Calcium Levels , 2005, Neuron.

[38]  D. Pinkel,et al.  Supporting Online Material Materials and Methods Figs. S1 and S2 Tables S1 and S2 References Combined Analog and Action Potential Coding in Hippocampal Mossy Fibers , 2022 .

[39]  G. Stuart,et al.  Site of Action Potential Initiation in Layer 5 Pyramidal Neurons , 2006, The Journal of Neuroscience.

[40]  J. DeFelipe,et al.  Voltage-gated ion channels in the axon initial segment of human cortical pyramidal cells and their relationship with chandelier cells. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[41]  D. Surmeier,et al.  Expression and biophysical properties of Kv1 channels in supragranular neocortical pyramidal neurones , 2006, The Journal of physiology.

[42]  D. McCormick,et al.  Modulation of intracortical synaptic potentials by presynaptic somatic membrane potential , 2006, Nature.

[43]  M. Gutnick,et al.  Persistent Sodium Current in Layer 5 Neocortical Neurons Is Primarily Generated in the Proximal Axon , 2006, The Journal of Neuroscience.

[44]  D. McCormick,et al.  Neurophysiology: Hodgkin and Huxley model — still standing? , 2007, Nature.

[45]  Yuguo Yu,et al.  Properties of action-potential initiation in neocortical pyramidal cells: evidence from whole cell axon recordings. , 2007, Journal of neurophysiology.

[46]  R. Rosenfeld Nature , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.