IA in Kenyon cells of the mushroom body of honeybees resembles shaker currents: kinetics, modulation by K+, and simulation.

Cultured Kenyon cells from the mushroom body of the honeybee, Apis mellifera, show a voltage-gated, fast transient K+ current that is sensitive to 4-aminopyridine, an A current. The kinetic properties of this A current and its modulation by extracellular K+ ions were investigated in vitro with the whole cell patch-clamp technique. The A current was isolated from other voltage-gated currents either pharmacologically or with suitable voltage-clamp protocols. Hodgkin- and Huxley-style mathematical equations were used for the description of this current and for the simulation of action potentials in a Kenyon cell model. Activation and inactivation of the A current are fast and voltage dependent with time constants of 0.4 +/- 0.1 ms (means +/- SE) at +45 mV and 3.0 +/- 1.6 ms at +45 mV, respectively. The pronounced voltage dependence of the inactivation kinetics indicates that at least a part of this current of the honeybee Kenyon cells is a shaker-like current. Deactivation and recovery from inactivation also show voltage dependency. The time constant of deactivation has a value of 0.4 +/- 0.1 ms at -75 mV. Recovery from inactivation needs a double-exponential function to be fitted adequately; the resulting time constants are 18 +/- 3.1 ms for the fast and 745 +/- 107 ms for the slow process at -75 mV. Half-maximal activation of the A current occurs at -0.7 +/- 2.9 mV, and half-maximal inactivation occurs at -54.7 +/- 2.4 mV. An increase in the extracellular K+ concentration increases the conductance and accelerates the recovery from inactivation of the A current, affecting the slow but not the fast time constant. With respect to these modulations the current under investigation resembles some of the shaker-like currents. The data of the A current were incorporated into a reduced computational model of the voltage-gated currents of Kenyon cells. In addition, the model contained a delayed rectifier K+ current, a Na+ current, and a leakage current. The model is able to generate an action potential on current injection. The model predicts that the A current causes repolarization of the action potential but not a delay in the initiation of the action potential. It further predicts that the activation of the delayed rectifier K+ current is too slow to contribute markedly to repolarization during a single action potential. Because of its fast activation, the A current reduces the amplitude of the net depolarizing current and thus reduces the peak amplitude and the duration of the action potential.

[1]  Allan R. Willms,et al.  Quantitative Single-Cell-Reverse Transcription-PCR Demonstrates That A-Current Magnitude Varies as a Linear Function ofshal Gene Expression in Identified Stomatogastric Neurons , 1997, The Journal of Neuroscience.

[2]  J. Byrne,et al.  Quantitative aspects of ionic conductance mechanisms contributing to firing pattern of motor cells mediating inking behavior in Aplysia californica. , 1980, Journal of neurophysiology.

[3]  L. Salkoff,et al.  Genetic analysis of Drosophila neurons: Shal, Shaw, and Shab encode most embryonic potassium currents , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[4]  R. W. Siegel,et al.  Drosophila mutations that alter ionic conduction disrupt acquisition and retention of a conditioned odor avoidance response. , 1986, Journal of neurogenetics.

[5]  O. Pongs,et al.  Shaker encodes a family of putative potassium channel proteins in the nervous system of Drosophila. , 1988, The EMBO journal.

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

[7]  P. Adams,et al.  Voltage-dependent currents of vertebrate neurons and their role in membrane excitability. , 1986, Advances in neurology.

[8]  R. Davis,et al.  Physiology and biochemistry of Drosophila learning mutants. , 1996, Physiological reviews.

[9]  C. Deutsch,et al.  Recovery from C-type inactivation is modulated by extracellular potassium. , 1996, Biophysical journal.

[10]  Y. Jan,et al.  Expression of functional potassium channels from Shaker cDNA in Xenopus oocytes , 1988, Nature.

[11]  J. Byrne.  Analysis of ionic conductance mechanisms in motor cells mediating inking behavior in Aplysia californica. , 1980, Journal of neurophysiology.

[12]  R. Menzel,et al.  Localization of short‐term memory in the brain of the bee, Apis mellifera , 1980 .

[13]  L. Salkoff,et al.  The drosophila shaker gene codes for a distinctive K+ current in a subset of neurons , 1990, Neuron.

[14]  G. Tseng,et al.  Differential effects of elevating [K]o on three transient outward potassium channels. Dependence on channel inactivation mechanisms. , 1992, Circulation research.

[15]  B. Rudy,et al.  A-type potassium channels expressed from Shaker locus cDNA. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[16]  B. Ganetzky,et al.  A potassium channel beta subunit related to the aldo-keto reductase superfamily is encoded by the Drosophila hyperkinetic locus. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[17]  C.‐F. Wu,et al.  Functional expression of Shaker K+ channels in cultured Drosophila "giant" neurons derived from Sh cDNA transformants: distinct properties, distribution, and turnover , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[18]  R. Keynes.  The ionic channels in excitable membranes. , 1975, Ciba Foundation symposium.

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

[20]  J. Trimmer,et al.  Differential spatiotemporal expression of K+ channel polypeptides in rat hippocampal neurons developing in situ and in vitro , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  Yuh Nung Jan,et al.  Evidence for the formation of heteromultimeric potassium channels in Xenopus oocytes , 1990, Nature.

[22]  M. Tanouye,et al.  Abnormal action potentials associated with the Shaker complex locus of Drosophila. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[23]  R. Wyman,et al.  Genetic modification of potassium channels in Drosophila Shaker mutants , 1981, Nature.

[24]  L. Pardo,et al.  Extracellular K+ specifically modulates a rat brain K+ channel. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[25]  R. Harris-Warrick,et al.  Physiological role of the transient potassium current in the pyloric circuit of the lobster stomatogastric ganglion. , 1992, Journal of neurophysiology.

[26]  Ronald L. Davis.  Mushroom bodies and drosophila learning , 1993, Neuron.

[27]  S. Demo,et al.  The inactivation gate of the Shaker K+ channel behaves like an open-channel blocker , 1991, Neuron.

[28]  N. Strausfeld,et al.  Subdivision of the drosophila mushroom bodies by enhancer-trap expression patterns , 1995, Neuron.

[29]  G. Yellen,et al.  Modulation of K+ current by frequency and external [K+]: A tale of two inactivation mechanisms , 1995, Neuron.

[30]  Y. Jan,et al.  Multiple potassium–channel components are produced by alternative splicing at the Shaker locus in Drosophila , 1988, Nature.

[31]  B. Rudy,et al.  Shaker K+ channel subunits from heteromultimeric channels with novel functional properties. , 1990, Biochemical and biophysical research communications.

[32]  A Borst,et al.  Drosophila mushroom body mutants are deficient in olfactory learning. , 1985, Journal of neurogenetics.

[33]  L. Salkoff,et al.  K+ current diversity is produced by an extended gene family conserved in Drosophila and mouse. , 1990, Science.

[34]  D. A. Baxter,et al.  Simulator for neural networks and action potentials: description and application. , 1994, Journal of neurophysiology.

[35]  Y. Jan,et al.  Multiple potassium-channel components are produced by alternative splicing at the shaker locus in Drosophila , 1988, Nature.

[36]  Y. Jan,et al.  Subcellular segregation of two A-type K+ channel proteins in rat central neurons , 1992, Neuron.

[37]  M. Tanouye,et al.  Multiple products of the drosophila Shaker gene may contribute to potassium channel diversity , 1988, Neuron.

[38]  R. Aldrich,et al.  Properties of ShB A-type potassium channels expressed in Shaker mutant Drosophila by germline transformation. , 1989, Neuron.

[39]  E. Kandel,et al.  Overexpression of an Aplysia shaker K+ channel gene modifies the electrical properties and synaptic efficacy of identified Aplysia neurons. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[40]  H. Guy,et al.  Structural Model of the Outer Vestibule and Selectivity Filter of the Shaker Voltage-gated K+ Channel , 1996, Neuropharmacology.

[41]  P. Mobbs.  The Brain of the Honeybee Apis Mellifera. I. The Connections and Spatial Organization of the Mushroom Bodies , 1982 .

[42]  Y. Zhong,et al.  Alteration of four identified K+ currents in Drosophila muscle by mutations in eag , 1991, Science.

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

[44]  Y. Jan,et al.  Cloning of genomic and complementary DNA from Shaker, a putative potassium channel gene from Drosophila. , 1987, Science.

[45]  J. Koester,et al.  The Role of K+ Currents in Frequency-Dependent Spike Broadening in Aplysia R20 Neurons: A Dynamic-Clamp Analysis , 1996, The Journal of Neuroscience.

[46]  D. Surmeier,et al.  Somatodendritic Depolarization-Activated Potassium Currents in Rat Neostriatal Cholinergic Interneurons Are Predominantly of the A Type and Attributable to Coexpression of Kv4.2 and Kv4.1 Subunits , 1998, The Journal of Neuroscience.

[47]  R. Hardie,et al.  Serotonin modulates the voltage dependence of delayed rectifier and Shaker potassium channels in drosophila photoreceptors , 1995, Neuron.

[48]  R Menzel,et al.  Ionic currents of Kenyon cells from the mushroom body of the honeybee , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[49]  K. Abromeit.  Music Received , 2023, Notes.

[50]  B. Hille.  Ionic channels of excitable membranes , 2001 .

[51]  B. Rudy,et al.  The role of the divergent amino and carboxyl domains on the inactivation properties of potassium channels derived from the Shaker gene of Drosophila , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[52]  R C Hardie,et al.  Voltage-sensitive potassium channels in Drosophila photoreceptors , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[53]  L. Salkoff,et al.  mShal, a subfamily of A-type K+ channel cloned from mammalian brain. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[54]  R. Aldrich,et al.  Properties of ShB AType potassium channels expressed in Shaker mutant drosophil by germline transformation , 1989, Neuron.

[55]  R. MacKinnon,et al.  Purification and characterization of three inhibitors of voltage-dependent K+ channels from Leiurus quinquestriatus var. hebraeus venom. , 1994, Biochemistry.

[56]  B. Ganetzky,et al.  Potassium currents in Drosophila: different components affected by mutations of two genes. , 1983, Science.

[57]  J. Koester,et al.  Consequences and mechanisms of spike broadening of R20 cells in Aplysia californica , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[58]  F. Tejedor,et al.  Diverse Expression and Distribution of ShakerPotassium Channels during the Development of the DrosophilaNervous System , 1997, The Journal of Neuroscience.

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

[60]  M. Hammer.  An identified neuron mediates the unconditioned stimulus in associative olfactory learning in honeybees , 1993, Nature.

[61]  O. Pongs,et al.  Molecular basis for different rates of recovery from inactivation in the Shaker potassium channel family , 1991, FEBS letters.

[62]  Y. Jan,et al.  Immunological characterization of K+ channel components from the Shaker locus and differential distribution of splicing variants in drosophila , 1990, Neuron.

[63]  C. Wu,et al.  In vivo functional role of the Drosophila hyperkinetic beta subunit in gating and inactivation of Shaker K+ channels. , 1996, Biophysical journal.

[64]  C. Stevens,et al.  Prediction of repetitive firing behaviour from voltage clamp data on an isolated neurone soma , 1971, The Journal of physiology.

[65]  J. Nerbonne,et al.  Myocardial potassium channels: electrophysiological and molecular diversity. , 1996, Annual review of physiology.

[66]  S. Kreissl,et al.  Dissociated neurons of the pupal honeybee brain in cell culture , 1992, Journal of neurocytology.

[67]  M. Covarrubias,et al.  K+ channel inactivation mediated by the concerted action of the cytoplasmic N- and C-terminal domains. , 1997, Biophysical journal.

[68]  M Heisenberg,et al.  Associative odor learning in Drosophila abolished by chemical ablation of mushroom bodies. , 1994, Science.