Dendrotoxin‐sensitive K+ currents contribute to accommodation in murine spiral ganglion neurons

We have previously identified two broad electrophysiological classes of spiral ganglion neuron that differ in their rate of accommodation ( Mo & Davis, 1997a ). In order to understand the underlying ionic basis of these characteristic firing patterns, we used α‐dendrotoxin (α‐DTX) to eliminate the contribution of a class of voltage‐gated K+ channels and assessed its effects on a variety of electrophysiological properties by using the whole‐cell configuration of the patch‐clamp technique. Exposure to α‐DTX caused neurons that initially displayed rapid accommodation to fire continuously during 240 ms depolarizing test pulses within a restricted voltage range. We found a non‐monotonic relationship between number of action potentials fired and membrane potential in the presence of α‐DTX that peaked at voltages between –40 to –10 mV and declined at more depolarized and hyperpolarized test potentials. The α‐DTX‐sensitive current had two components that activated in different voltage ranges. Analysis of recordings made from acutely isolated neurons gave estimated half‐maximal activation voltages of –63 and 12 mV for the two components. Because α‐DTX blocks the Kv1.1, Kv1.2 and Kv1.6 subunits, we examined the action of the Kv1.1‐selective blocker dendrotoxin K (DTX‐K). We found that this antagonist reproduced the effects of α‐DTX on neuronal firing, and that the DTX‐K‐sensitive current also had two separate components. These data suggest that the transformation from a rapidly adapting to a slowly adapting firing pattern was mediated by the low voltage‐activated component of DTX‐sensitive current with a potential contribution from the high voltage‐activated component at more depolarized potentials. In addition, the effects of DTX‐K indicate that Kv1.1 subunits are important constituents of the underlying voltage‐gated potassium channels.

[1]  T. Moser,et al.  The Presynaptic Function of Mouse Cochlear Inner Hair Cells during Development of Hearing , 2001, The Journal of Neuroscience.

[2]  D. Oertel The role of timing in the brain stem auditory nuclei of vertebrates. , 1999, Annual review of physiology.

[3]  T. Furukawa,et al.  Adaptive rundown of excitatory post‐synaptic potentials at synapses between hair cells and eight nerve fibres in the goldfish. , 1978, The Journal of physiology.

[4]  J. Santos-Sacchi,et al.  Voltage-dependent ionic conductances of type I spiral ganglion cells from the guinea pig inner ear , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  R. Davis Differential distribution of potassium channels in acutely demyelinated, primary-auditory neurons in vitro. , 1996, Journal of neurophysiology.

[6]  I. Whitfield Discharge Patterns of Single Fibers in the Cat's Auditory Nerve , 1966 .

[7]  B. Lütkenhöner,et al.  Rapid adaptation of auditory-nerve fibers: Fine structure at high stimulus intensities , 1986, Hearing Research.

[8]  R. Davis,et al.  Endogenous firing patterns of murine spiral ganglion neurons. , 1997, Journal of neurophysiology.

[9]  C. Mulle,et al.  Early stages of myelination in the spiral ganglion cells of the kitten during development. , 1980, Acta oto-laryngologica.

[10]  B. Tempel,et al.  Expression of Kv1.1, a Shaker-Like Potassium Channel, Is Temporally Regulated in Embryonic Neurons and Glia , 1998, The Journal of Neuroscience.

[11]  A. Harvey,et al.  Twenty years of dendrotoxins. , 2001, Toxicon : official journal of the International Society on Toxinology.

[12]  S. Chiu,et al.  Analysis of potassium channel functions in mammalian axons by gene knockouts , 1999, Journal of neurocytology.

[13]  R. Davis,et al.  Heterogeneous voltage dependence of inward rectifier currents in spiral ganglion neurons. , 1997, Journal of neurophysiology.

[14]  L. A. Westerman,et al.  Rapid adaptation depends on the characteristic frequency of auditory nerve fibers , 1985, Hearing Research.

[15]  O. Pongs,et al.  Immunohistochemical Localization of Five Members of the KV1 Channel Subunits: Contrasting Subcellular Locations and Neuron‐specific Co‐localizations in Rat Brain , 1995, The European journal of neuroscience.

[16]  L. Kaczmarek,et al.  Contribution of the Kv3.1 potassium channel to high‐frequency firing in mouse auditory neurones , 1998, The Journal of physiology.

[17]  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.

[18]  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.

[19]  I. Forsythe,et al.  The binaural auditory pathway: membrane currents limiting multiple action potential generation in the rat medial nucleus of the trapezoid body , 1993, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[20]  P. Schwartzkroin,et al.  Heteromultimeric K+ channels in terminal and juxtaparanodal regions of neurons , 1993, Nature.

[21]  T. Moser,et al.  Kinetics of exocytosis and endocytosis at the cochlear inner hair cell afferent synapse of the mouse. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[22]  B. Robertson,et al.  The relative potencies of dendrotoxins as blockers of the cloned voltage‐gated K+ channel, mKv1.1 (MK‐1), when stably expressed in Chinese hamster ovary cells , 1997, British journal of pharmacology.

[23]  P. H. Smith,et al.  Intracellular recordings from neurobiotin-labeled cells in brain slices of the rat medial nucleus of the trapezoid body , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[24]  M. Goycoolea,et al.  Ultrastructural studies of the peripheral extensions (dendrites) of type i ganglion cells in the cat , 1990, The Laryngoscope.

[25]  E. Barrett,et al.  Electrical and morphological factors influencing the depolarizing after‐potential in rat and lizard myelinated axons. , 1995, The Journal of physiology.

[26]  Mario A. Ruggero,et al.  Physiology and Coding of Sound in the Auditory Nerve , 1992 .

[27]  T. Furukawa,et al.  Neurophysiological studies on hearing in goldfish. , 1967, Journal of neurophysiology.

[28]  G. Gamkrelidze,et al.  Potassium currents and excitability in second‐order auditory and vestibular neurons , 1998, Journal of neuroscience research.

[29]  S. Chiu,et al.  Determinants of Excitability at Transition Zones in Kv1.1-Deficient Myelinated Nerves , 1999, The Journal of Neuroscience.

[30]  A. Reyes,et al.  Membrane properties underlying the firing of neurons in the avian cochlear nucleus , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[31]  S. Chiu,et al.  Temperature-Sensitive Neuromuscular Transmission in Kv1.1 Null Mice: Role of Potassium Channels under the Myelin Sheath in Young Nerves , 1998, The Journal of Neuroscience.

[32]  R. Romand,et al.  Perinatal growth of spiral ganglion cells in the kitten , 1986, Hearing Research.

[33]  M. Schwartz,et al.  Stabilization of neurofilament transcripts during postnatal development. , 1994, Brain research. Molecular brain research.

[34]  M. Cynader,et al.  The correlation between cortical neuron maturation and neurofilament phosphorylation: a developmental study of phosphorylated 200 kDa neurofilament protein in cat visual cortex. , 1994, Brain research. Developmental brain research.

[35]  D. Oertel,et al.  Potassium currents in octopus cells of the mammalian cochlear nucleus. , 2001, Journal of neurophysiology.

[36]  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.

[37]  David Kay Ryugo,et al.  The Auditory Nerve: Peripheral Innervation, Cell Body Morphology, and Central Projections , 1992 .

[38]  J. Trimmer,et al.  K+ channel distribution and clustering in developing and hypomyelinated axons of the optic nerve , 1999, Journal of neurocytology.

[39]  R. Romand,et al.  Development of spiral ganglion cells in mammalian cochlea. , 1990, Journal of electron microscopy technique.

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

[41]  W. S. Rhode,et al.  Characteristics of tone-pip response patterns in relationship to spontaneous rate in cat auditory nerve fibers , 1985, Hearing Research.

[42]  Chu Chen,et al.  Hyperpolarization-activated current (I h) in primary auditory neurons , 1997, Hearing Research.

[43]  L. A. Westerman,et al.  Rapid and short-term adaptation in auditory nerve responses , 1984, Hearing Research.

[44]  P. Manis,et al.  Outward currents in isolated ventral cochlear nucleus neurons , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[45]  B. Sakmann,et al.  Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches , 1981, Pflügers Archiv.

[46]  Alexander Joseph Book reviewDischarge patterns of single fibers in the cat's auditory nerve: Nelson Yuan-Sheng Kiang, with the assistance of Takeshi Watanabe, Eleanor C. Thomas and Louise F. Clark: Research Monograph no. 35. Cambridge, Mass., The M.I.T. Press, 1965 , 1967 .

[47]  A. Fox,et al.  Multiple Ca2+ currents elicited by action potential waveforms in acutely isolated adult rat dorsal root ganglion neurons , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[48]  W. F. Hopkins,et al.  Properties of voltage-gated K+ currents expressed inXenopus oocytes by mKv1.1, mKv1.2 and their heteromultimers as revealed by mutagenesis of the dendrotoxin-binding site in mKv1.1 , 1994, Pflügers Archiv.

[49]  L. Trussell,et al.  Characterization of outward currents in neurons of the avian nucleus magnocellularis. , 1998, Journal of neurophysiology.

[50]  E. Guatteo,et al.  Action potentials recorded with patch-clamp amplifiers: are they genuine? , 1996, Trends in Neurosciences.

[51]  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.

[52]  R L Davis,et al.  Synergistic effects of BDNF and NT‐3 on postnatal spiral ganglion neurons , 1997, The Journal of comparative neurology.

[53]  H. Brew,et al.  Differential expression of voltage-gated potassium channel genes in auditory nuclei of the mouse brainstem , 2000, Hearing Research.

[54]  P. H. Smith,et al.  Structural and functional differences distinguish principal from nonprincipal cells in the guinea pig MSO slice. , 1995, Journal of neurophysiology.

[55]  G. Gamkrelidze,et al.  The Differential Expression of Low-Threshold Sustained Potassium Current Contributes to the Distinct Firing Patterns in Embryonic Central Vestibular Neurons , 1998, The Journal of Neuroscience.

[56]  R. Romand,et al.  The ultrastructure of spiral ganglion cells in the mouse. , 1987, Acta oto-laryngologica.

[57]  D. Robertson Possible relation between structure and spike shapes of neurones in guinea pig cochlear ganglion , 1976, Brain Research.

[58]  Hao Wang,et al.  Deletion of the KV1.1 Potassium Channel Causes Epilepsy in Mice , 1998, Neuron.

[59]  Dipesh Risal,et al.  Dynamic Potassium Channel Distributions during Axonal Development Prevent Aberrant Firing Patterns , 1999, The Journal of Neuroscience.

[60]  E Wanke,et al.  Modalities of distortion of physiological voltage signals by patch-clamp amplifiers: a modeling study. , 1998, Biophysical journal.

[61]  Xi Lin Action potentials and underlying voltage-dependent currents studied in cultured spiral ganglion neurons of the postnatal gerbil , 1997, Hearing Research.

[62]  K. Sanders,et al.  Functional and molecular expression of a voltage‐dependent K+ channel (Kv1.1) in interstitial cells of Cajal , 2001, The Journal of physiology.

[63]  S. Chiu,et al.  Myelinating Schwann cells determine the internodal localization of Kv1.1, Kv1.2, Kvβ2, and Caspr , 1999, Journal of neurocytology.

[64]  E. Barrett,et al.  Activation of internodal potassium conductance in rat myelinated axons. , 1993, The Journal of physiology.

[65]  N. Ogata,et al.  A simple and multi-purpose “concentration-clamp” method for rapid superfusion , 1991, Journal of Neuroscience Methods.

[66]  Donata Oertel,et al.  Maturation of synapses and electrical properties of cells in the cochlear nuclei , 1987, Hearing Research.

[67]  Laurence O Trussell,et al.  Cellular mechanisms for preservation of timing in central auditory pathways , 1997, Current Opinion in Neurobiology.

[68]  X. Lin,et al.  Endogenously generated spontaneous spiking activities recorded from postnatal spiral ganglion neurons in vitro. , 2000, Brain research. Developmental brain research.

[69]  Donald Robertson,et al.  Very rapid adaptation in the guinea pig auditory nerve , 1985, Hearing Research.

[70]  I. Forsythe,et al.  Two voltage-dependent K+ conductances with complementary functions in postsynaptic integration at a central auditory synapse , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.