A novel tetrodotoxin-insensitive, slow sodium current in striatal and hippocampal beurons

Slow inward currents modulate neuronal firing patterns and may generate depolarizing afterpotentials (DAPs). We report a novel, slow Na+ current (INaS) in striatal and hippocampal neurons that can generate DAPs. INaS activated at depolarizations greater than -40 mV, was tetrodotoxin insensitive, and activated and deactivated slowly over hundreds of milliseconds. INaS was dependent upon extracellular Na+, but was not affected by 0 mM extracellular Ca2+ or by Ca2+ channel blockers (Mn2+, Cd2+, or Co2+). A tetrodotoxin-insensitive, Na(+)-dependent plateau potential that was likely generated by INaS was shown to underlie DAPs during intracellular recordings from hippocampal CA1 pyramidal neurons. Membrane depolarizations and DAPs generated by INaS may contribute to alterations in neuronal firing and epileptiform bursting.

[1]  A. Brown,et al.  Voltage clamp and internal perfusion of single rat heart muscle cells. , 1981, The Journal of physiology.

[2]  S. Waxman,et al.  Non-synaptic mechanisms of Ca2+-mediated injury in CNS white matter , 1991, Trends in Neurosciences.

[3]  Stephen J. Smith,et al.  Current-voltage relationships of repetitively firing neurons , 1979, Brain Research.

[4]  R. Tsien,et al.  Mechanism of ion permeation through calcium channels , 1984, Nature.

[5]  R. Llinás The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function. , 1988, Science.

[6]  D. Prince,et al.  Developmental changes in Na+ conductances in rat neocortical neurons: appearance of a slowly inactivating component. , 1988, Journal of neurophysiology.

[7]  R K Wong,et al.  Calcium current activation kinetics in isolated pyramidal neurones of the Ca1 region of the mature guinea‐pig hippocampus. , 1987, The Journal of physiology.

[8]  Y. Shimada,et al.  Tetrodotoxin‐resistant electric activity in chick skeletal muscle cells differentiated in vitro , 1973, Journal of cellular physiology.

[9]  A. Samejima,et al.  Tetrodotoxin-resistant sodium and calcium components of action potentials in dorsal root ganglion cells of the adult mouse. , 1978, Journal of neurophysiology.

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

[11]  Robert K. S. Wong,et al.  Isolation of neurons suitable for patch-clamping from adult mammalian central nervous systems , 1986, Journal of Neuroscience Methods.

[12]  P. Schwindt,et al.  Negative slope conductance due to a persistent subthreshold sodium current in cat neocortical neurons in vitro , 1982, Brain Research.

[13]  P. G. Kostyuk,et al.  Ionic currents in the somatic membrane of rat dorsal root ganglion neurons—I. Sodium currents , 1981, Neuroscience.

[14]  R. North,et al.  Membrane properties and synaptic responses of rat striatal neurones in vitro. , 1991, The Journal of physiology.

[15]  S. Franceschetti,et al.  Effects of anticonvulsants on spontaneous epileptiform activity which develops in the absence of chemical synaptic transmission in hippocampal slices , 1985, Brain Research.

[16]  B. MacVicar Depolarizing prepotentials are Na+ dependent in CA1 pyramidal neurons , 1985, Brain Research.

[17]  R. Llinás,et al.  Subthreshold Na+-dependent theta-like rhythmicity in stellate cells of entorhinal cortex layer II , 1989, Nature.

[18]  B. R. Gallego The ionic basis of action potentials in petrosal ganglion cells of the cat. , 1983, The Journal of physiology.

[19]  R K Wong,et al.  Afterpotential generation in hippocampal pyramidal cells. , 1981, Journal of neurophysiology.

[20]  A. Konnerth,et al.  Slow transmission of neural activity in hippocampal area CA1 in absence of active chemical synapses , 1984, Nature.

[21]  R. Horn,et al.  Functional differences between two classes of sodium channels in developing rat skeletal muscle. , 1986, Science.

[22]  B. MacVicar,et al.  Multiple types of calcium channels in acutely isolated rat neostriatal neurons , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  R. Rogart,et al.  Primary structure and expression of a sodium channel characteristic of denervated and immature rat skeletal muscle , 1990, Neuron.

[24]  H. Haas,et al.  Synchronized bursting of CA1 hippocampal pyramidal cells in the absence of synaptic transmission , 1982, Nature.

[25]  F. Dudek,et al.  Synchronization without active chemical synapses during hippocampal afterdischarges. , 1984, Journal of neurophysiology.

[26]  B. Connors,et al.  Electrophysiological properties of neocortical neurons in vitro. , 1982, Journal of neurophysiology.

[27]  F. Dudek,et al.  Excitation of hippocampal pyramidal cells by an electrical field effect. , 1984, Journal of neurophysiology.

[28]  F. Dudek,et al.  Synchronous neural afterdischarges in rat hippocampal slices without active chemical synapses. , 1982, Science.

[29]  G. Aghajanian,et al.  Excitation of locus coeruleus neurons by vasoactive intestinal peptide: role of a cAMP and protein kinase A , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[30]  G Bernardi,et al.  Synaptic and intrinsic control of membrane excitability of neostriatal neurons. I. An in vivo analysis. , 1990, Journal of neurophysiology.

[31]  A. Friedman,et al.  Low-threshold calcium electrogenesis in neocortical neurons , 1987, Neuroscience Letters.

[32]  A. Friedman,et al.  Slow depolarizing afterpotentials in neocortical neurons are sodium and calcium dependent , 1992, Neuroscience Letters.

[33]  G. Schofield,et al.  Tetrodotoxin‐resistant sodium current of rat nodose neurones: monovalent cation selectivity and divalent cation block. , 1987, The Journal of physiology.

[34]  J. Bossu,et al.  Patch-clamp study of the tetrodotoxin-resistant sodium current in group C sensory neurones , 1984, Neuroscience Letters.

[35]  P. Calabresi,et al.  Intracellular studies on the dopamine-induced firing inhibition of neostriatal neurons in vitro: Evidence for D1 receptor involvement , 1987, Neuroscience.

[36]  A. Brown,et al.  Trypsin inhibits the action of tetrodotoxin on neurones , 1977, Nature.

[37]  R. Gillette,et al.  Patch- and voltage-clamp analysis of cyclic AMP-stimulated inward current underlying neurone bursting , 1983, Nature.

[38]  R. Traub Simulation of intrinsic bursting in CA3 hippocampal neurons , 1982, Neuroscience.

[39]  M. Raggenbass,et al.  Vasopressin generates a persistent voltage-dependent sodium current in a mammalian motoneuron , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[40]  R. Llinás,et al.  Electrophysiological properties of in vitro Purkinje cell dendrites in mammalian cerebellar slices. , 1980, The Journal of physiology.

[41]  P. Gage,et al.  A threshold sodium current in pyramidal cells in rat hippocampus , 1985, Neuroscience Letters.

[42]  P. Schwindt,et al.  Properties of persistent sodium conductance and calcium conductance of layer V neurons from cat sensorimotor cortex in vitro. , 1985, Journal of neurophysiology.

[43]  A. Konnerth,et al.  Ionic Properties of Burst Generation in Hippocampal Pyramidal Cell Somata ‘In Vitro’ , 1986 .

[44]  T. Nagao,et al.  Cyclic AMP analog activates Na+-dependent inward currents in dissociated frog motoneurons , 1992, Brain Research.

[45]  J. Connor,et al.  A novel membrane sodium current induced by injection of cyclic nucleotides into gastropod neurones. , 1984, The Journal of physiology.

[46]  W. Almers,et al.  Non‐selective conductance in calcium channels of frog muscle: calcium selectivity in a single‐file pore. , 1984, The Journal of physiology.

[47]  W. Almers,et al.  A non‐selective cation conductance in frog muscle membrane blocked by micromolar external calcium ions. , 1984, The Journal of physiology.

[48]  E. Kandel,et al.  Electrophysiology of hippocampal neurons. II. After-potentials and repetitive firing. , 1961, Journal of neurophysiology.

[49]  N. Spitzer On the basis of delayed depolarization and its role in repetitive firing of Rohon‐Beard neurones in Xenopus tadpoles. , 1984, The Journal of physiology.

[50]  F. Bezanilla,et al.  Destruction of Sodium Conductance Inactivation in Squid Axons Perfused with Pronase , 1973, The Journal of general physiology.

[51]  R. Eckert,et al.  A voltage‐sensitive persistent calcium conductance in neuronal somata of Helix. , 1976, The Journal of physiology.

[52]  D. Lewis Spike aftercurrents in R15 of Aplysia: their relationship to slow inward current and calcium influx. , 1984, Journal of neurophysiology.

[53]  H Wachtel,et al.  Negative Resistance Characteristic Essential for the Maintenance of Slow Oscillations in Bursting Neurons , 1974, Science.

[54]  D. Prince,et al.  Burst generating and regular spiking layer 5 pyramidal neurons of rat neocortex have different morphological features , 1990, The Journal of comparative neurology.

[55]  D. Prince,et al.  Electrophysiology of isolated hippocampal pyramidal dendrites , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[56]  S. J. Smith,et al.  Depolarizing afterpotentials and burst production in molluscan pacemaker neurons. , 1976, Journal of neurophysiology.

[57]  P. Calabresi,et al.  Intrinsic membrane properties of neostriatal neurons can account for their low level of spontaneous activity , 1987, Neuroscience.

[58]  R. Llinás,et al.  Ionic basis for the electro‐responsiveness and oscillatory properties of guinea‐pig thalamic neurones in vitro. , 1984, The Journal of physiology.

[59]  R. Rogart,et al.  Molecular cloning of a putative tetrodotoxin-resistant rat heart Na+ channel isoform. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[60]  D. Prince,et al.  Printed in Great Britain , 2005 .

[61]  P W Gage,et al.  A voltage-dependent persistent sodium current in mammalian hippocampal neurons , 1990, The Journal of general physiology.

[62]  D. Kernell,et al.  Delayed depolarization and the repetitive response to intracellular stimulation of mammalian motoneurones , 1963, The Journal of physiology.

[63]  T. Narahashi,et al.  Differential properties of tetrodotoxin-sensitive and tetrodotoxin- resistant sodium channels in rat dorsal root ganglion neurons , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.