Transient Potassium Currents Regulate the Discharge Patterns of Dorsal Cochlear Nucleus Pyramidal Cells

Pyramidal cells in the dorsal cochlear nucleus (DCN) show three distinct temporal discharge patterns in response to sound: “pauser,” “buildup,” and “chopper.” Similar discharge patterns are seen in vitro and depend on the voltage from which the cell is depolarized. It has been proposed that an inactivating A-type K+ current (IKI) might play a critical role in generating the three different patterns. In this study we examined the characteristics of transient currents in DCN pyramidal cells to evaluate this hypothesis. Morphologically identified pyramidal cells in rat brain slices (P11–P17) exhibited the three voltage-dependent discharge patterns. Two inactivating currents were present in outside-out patches from pyramidal cells: a rapidly inactivating (IKIF, τ ∼11 msec) current insensitive to block by tetraethylammonium (TEA) and variably blocked by 4-aminopyridine (4-AP) with half-inactivation near −85 mV, and a slowly inactivating TEA- and 4-AP-sensitive current (IKIS, τ ∼145 msec) with half-inactivation near −35 mV. Recovery from inactivation at 34°C was described by a single exponential with a time constant of 10–30 msec, similar to the rate at which first spike latency increases with the duration of a hyperpolarizing prepulse. Acutely isolated cells also possessed a rapidly activating (<1 msec at 22°C) transient current that activated near −45 mV and showed half-inactivation near −80 mV. A model demonstrated that the deinactivation ofIKIF was correlated with the discharge patterns. Overall, the properties of the fast inactivating K+ current were consistent with their proposed role in shaping the discharge pattern of DCN pyramidal cells.

[1]  T. J. Baldwin,et al.  Characterization of a mammalian cDNA for an inactivating voltage-sensitive K+ channel , 1991, Neuron.

[2]  Potassium currents in rat cerebellar Purkinje neurones maintained in culture in L15 (Leibovitz) medium , 1988, Neuroscience Letters.

[3]  Lateral and Medial Olivocochlear Neurons Have Distinct Electrophysiological Properties in the Rat Brain Slice(ラット蝸牛遠心性ニューロン(オリーブ核蝸牛ニューロン)の電気生理学特性に関する研究) , 1998 .

[4]  E. Ağar,,et al.  Membrane Properties of Mouse Dorsal Cochlear Nucleus Neurons in Vitro , 1997, Journal of basic and clinical physiology and pharmacology.

[5]  B. Rudy,et al.  Differential expression of Shaw-related K+ channels in the rat central nervous system , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[6]  M A Rogawski,et al.  A transient potassium conductance regulates the excitability of cultured hippocampal and spinal neurons , 1984, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[7]  B. Rudy,et al.  Diversity and ubiquity of K channels , 1988, Neuroscience.

[8]  B. Rudy,et al.  Cloning of ShIII (Shaw-like) cDNAs encoding a novel high-voltage-activating, TEA-sensitive, type-A K+ channel , 1992, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[9]  E D Young,et al.  Effects of somatosensory and parallel-fiber stimulation on neurons in dorsal cochlear nucleus. , 1996, Journal of neurophysiology.

[10]  A computer model of dorsal cochlear nucleus pyramidal cells: intrinsic membrane properties. , 1995, The Journal of the Acoustical Society of America.

[11]  B. Rudy,et al.  Identification of molecular components of A-type channels activating at subthreshold potentials. , 1994, Journal of neurophysiology.

[12]  J. A. Hirsch,et al.  Intrinsic properties of neurones in the dorsal cochlear nucleus of mice, in vitro. , 1988, The Journal of physiology.

[13]  J. Connor,et al.  Neural repetitive firing: modifications of the Hodgkin-Huxley axon suggested by experimental results from crustacean axons. , 1977, Biophysical journal.

[14]  S Nakajima,et al.  Acetylcholine raises excitability by inhibiting the fast transient potassium current in cultured hippocampal neurons. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[15]  C. Stevens,et al.  Voltage clamp studies of a transient outward membrane current in gastropod neural somata , 1971, The Journal of physiology.

[16]  E D Young,et al.  Somatosensory effects on neurons in dorsal cochlear nucleus. , 1995, Journal of neurophysiology.

[17]  R. Aldrich,et al.  Single-channel and genetic analyses reveal two distinct A-type potassium channels in Drosophila. , 1987, Science.

[18]  H. Voigt,et al.  Cross-correlation analysis of inhibitory interactions in dorsal cochlear nucleus. , 1990, Journal of neurophysiology.

[19]  D A Godfrey,et al.  Single unit activity in the dorsal cochlear nucleus of the cat , 1975, The Journal of comparative neurology.

[20]  W. S. Rhode,et al.  Physiological response properties of cells labeled intracellularly with horseradish peroxidase in cat dorsal cochlear nucleus , 1983, The Journal of comparative neurology.

[21]  J. Barker,et al.  Rat hippocampal neurons in culture: potassium conductances. , 1984, Journal of neurophysiology.

[22]  H. Voigt,et al.  Evidence of inhibitory interactions between neurons in dorsal cochlear nucleus. , 1980, Journal of neurophysiology.

[23]  S. Thompson Aminopyridine block of transient potassium current , 1982, The Journal of general physiology.

[24]  U. Heinemann,et al.  Comparison of voltage-dependent potassium currents in rat pyramidal neurons acutely isolated from hippocampal regions CA1 and CA3. , 1995, Journal of neurophysiology.

[25]  PB Manis,et al.  Membrane properties and discharge characteristics of guinea pig dorsal cochlear nucleus neurons studied in vitro , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

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

[27]  K. Koyano,et al.  Lateral and medial olivocochlear neurons have distinct electrophysiological properties in the rat brain slice. , 1997, Journal of neurophysiology.

[28]  W. Nonner,et al.  Transient K current in the somatic membrane of cultured central neurons of embryonic rat. , 1992, Journal of neurophysiology.

[29]  S. Zhang,et al.  Neuronal circuits associated with the output of the dorsal cochlear nucleus through fusiform cells. , 1994, Journal of neurophysiology.

[30]  D Bertrand,et al.  DATAC: a multipurpose biological data analysis program based on a mathematical interpreter. , 1986, International journal of bio-medical computing.

[31]  Stefan H. Heinemann,et al.  Regulation of fast inactivation of cloned mammalian IK(A) channels by cysteine oxidation , 1991, Nature.

[32]  B. Rudy,et al.  Differential expression of Kv4 K+ channel subunits mediating subthreshold transient K+ (A-type) currents in rat brain. , 1998, Journal of neurophysiology.

[33]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1990 .

[34]  M. Lazdunski,et al.  Susceptibility of cloned K+ channels to reactive oxygen species. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[35]  C. Bader,et al.  Voltage‐dependent potassium currents in developing neurones from quail mesencephalic neural crest. , 1985, The Journal of physiology.

[36]  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.

[37]  B. Rudy,et al.  Cloning of a novel component of A-type K+ channels operating at subthreshold potentials with unique expression in heart and brain. , 1996, Journal of neurophysiology.

[38]  H. Wigström,et al.  A transient outward current in a mammalian central neurone blocked by 4-aminopyridine , 1982, Nature.

[39]  G. Spirou,et al.  Physiology and morphology of complex spiking neurons in the guinea pig dorsal cochlear nucleus , 1994, The Journal of comparative neurology.

[40]  R K Wong,et al.  Outward currents of single hippocampal cells obtained from the adult guinea‐pig. , 1987, The Journal of physiology.

[41]  D. Ryugo,et al.  The dorsal cochlear nucleus of the mouse: A light microscopic analysis of neurons that project to the inferior colliculus , 1985, The Journal of comparative neurology.

[42]  B. Rudy,et al.  Cloning of a human cDNA expressing a high voltage‐activating. Tea‐sensitive, type‐a K+ channel which maps to chromosome 1 band p21 , 1991, Journal of neuroscience research.

[43]  P. Schwindt,et al.  Multiple potassium conductances and their functions in neurons from cat sensorimotor cortex in vitro. , 1988, Journal of neurophysiology.

[44]  D. K. Morest,et al.  The neuronal architecture of the cochlear nucleus of the cat , 1974, The Journal of comparative neurology.

[45]  I. Forsythe,et al.  Membrane Currents Influencing Action Potential Latency in Granule Neurons of the Rat Cochlear Nucleus , 1997, The European journal of neuroscience.

[46]  T. Blackstad,et al.  Pyramidal neurones of the dorsal cochlear nucleus: A golgi and computer reconstruction study in cat , 1984, Neuroscience.

[47]  J. Ruppersberg,et al.  Cloning and functional expression of a TEA‐sensitive A‐type potassium channel from rat brain , 1991, FEBS letters.

[48]  L. Wang,et al.  Activation of Kv3.1 channels in neuronal spine-like structures may induce local potassium ion depletion. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[49]  P. Schwindt,et al.  Differential effects of TEA and cations on outward ionic currents of cat motoneurons. , 1981, Journal of neurophysiology.