Sodium Current in Rat and Cat Thalamocortical Neurons: Role of a Non-Inactivating Component in Tonic and Burst Firing

The properties of the Na+ current present in thalamocortical neurons of the dorsal lateral geniculate nucleus were investigated in dissociated neonate rat and cat neurons and in neurons from slices of neonate and adult rats using patch and sharp electrode recordings. The steady-state activation and inactivation of the transient Na+ current (INa) was well fitted with a Boltzmann curve (voltage of half-maximal activation and inactivation, V1/2, −29.84 mV and −70.04 mV, respectively). Steady-state activation and inactivation curves showed a small region of overlap, indicating the occurrence of a INa window current.INa decay could be fitted with a single exponential function, consistent with the presence of only one channel type. Voltage ramp and step protocols showed the presence of a noninactivating component of the Na+ current (INaP) that activated at potentials more negative (V1/2 = −56.93 mV) than those of INa. The maximal amplitude ofINaP was ∼2.5% ofINa, thus significantly greater than the calculated contribution (0.2%) of theINa window component. Comparison of results from dissociated neurons and neurons in slices suggested a dendritic as well as a somatic localization of INaP. Inclusion of papain in the patch electrode removed the fast inactivation of INa and induced a current with voltage-dependence (V1/2 = −56.92) and activation parameters similar to those ofINaP. Current-clamp recordings with sharp electrodes showed thatINaP contributed to depolarizations evoked from potentials of approximately −60 mV and unexpectedly to the amplitude and latency of low-threshold Ca2+potentials, suggesting that this noninactivating component of the Na+ channel population plays an important role in the integrative properties of thalamocortical neurons during both tonic and burst-firing patterns.

[1]  Differences in voltage-dependent sodium currents exhibited by superficial and deep layer neurons of guinea pig entorhinal cortex. , 1994, Journal of neurophysiology.

[2]  D. Prince,et al.  Intrathalamic rhythmicity studied in vitro: nominal T-current modulation causes robust antioscillatory effects , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[3]  A. Constanti,et al.  Mechanism of block by ZD 7288 of the hyperpolarization-activated inward rectifying current in guinea pig substantia nigra neurons in vitro. , 1995, Journal of neurophysiology.

[4]  E. Puil,et al.  Mechanisms for signal transformation in lemniscal auditory thalamus. , 1996, Journal of neurophysiology.

[5]  N. Leresche Synaptic Currents in Thalamo‐cortical Neurons of the Rat Lateral Geniculate Nucleus , 1992, The European journal of neuroscience.

[6]  M. Pirchio,et al.  The ventral and dorsal lateral geniculate nucleus of the rat: intracellular recordings in vitro. , 1987, The Journal of physiology.

[7]  A. Hernández-Cruz,et al.  Identification of two calcium currents in acutely dissociated neurons from the rat lateral geniculate nucleus. , 1989, Journal of neurophysiology.

[8]  H Bostock,et al.  Low-threshold, persistent sodium current in rat large dorsal root ganglion neurons in culture. , 1997, Journal of neurophysiology.

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

[10]  H. Takeshima,et al.  Existence of distinct sodium channel messenger RNAs in rat brain , 1986, Nature.

[11]  P W Gage,et al.  The sodium current underlying action potentials in guinea pig hippocampal CA1 neurons , 1988, The Journal of general physiology.

[12]  B W Connors,et al.  Intrinsic neuronal physiology and the functions, dysfunctions and development of neocortex. , 1994, Progress in brain research.

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

[14]  R. Llinás,et al.  Electrophysiological properties of guinea‐pig thalamic neurones: an in vitro study. , 1984, The Journal of physiology.

[15]  P. Schwindt,et al.  Different voltage dependence of transient and persistent Na+ currents is compatible with modal-gating hypothesis for sodium channels. , 1994, Journal of neurophysiology.

[16]  H. Pape,et al.  Different Types of Potassium Outward Current in Relay Neurons Acutely Isolated from the Rat Lateral Geniculate Nucleus , 1992, The European journal of neuroscience.

[17]  E. Puil,et al.  Mode of firing and rectifying properties of nucleus ovoidalis neurons in the avian auditory thalamus. , 1994, Journal of neurophysiology.

[18]  C. Alzheimer,et al.  A novel voltage‐dependent cation current in rat neocortical neurones. , 1994, The Journal of physiology.

[19]  P. Adams,et al.  Visualization of calcium influx through channels that shape the burst and tonic firing modes of thalamic relay cells. , 1997, Journal of neurophysiology.

[20]  D. Barth,et al.  Thalamic modulation of high-frequency oscillating potentials in auditory cortex , 1996, Nature.

[21]  P. Gage,et al.  A persistent sodium current in rat ventricular myocytes. , 1992, The Journal of physiology.

[22]  E. G. Jones,et al.  Thalamic oscillations and signaling , 1990 .

[23]  R. Llinás,et al.  Dendritic calcium conductances generate high-frequency oscillation in thalamocortical neurons. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[24]  I. Ebenezer Effects of the 5HT1A agonist, 8-OH-DPAT, on operant food intake in non-deprived rats. , 1992, Neuroreport.

[25]  C. Armstrong,et al.  Analysis of sodium channel tail currents. , 1992, Methods in enzymology.

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

[27]  George L. Gerstein,et al.  Feature-linked synchronization of thalamic relay cell firing induced by feedback from the visual cortex , 1994, Nature.

[28]  R. Traub,et al.  Neuronal Networks of the Hippocampus , 1991 .

[29]  B. Connors,et al.  Intrinsic oscillations of neocortex generated by layer 5 pyramidal neurons. , 1991, Science.

[30]  D. Contreras,et al.  Electrophysiological properties of intralaminar thalamocortical cells discharging rhythmic (approximately 40 HZ) spike-bursts at approximately 1000 HZ during waking and rapid eye movement sleep. , 1993, Neuroscience.

[31]  K. D. Singh,et al.  Magnetic field tomography of coherent thalamocortical 40-Hz oscillations in humans. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[32]  D. Contreras,et al.  Electrophysiological properties of intralaminar thalamocortical cells discharging rhythmic (≈40 HZ) spike-bursts at ≈1000 HZ during waking and rapid eye movement sleep , 1993, Neuroscience.

[33]  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.

[34]  D. Johnston,et al.  Characterization of single voltage‐gated Na+ and Ca2+ channels in apical dendrites of rat CA1 pyramidal neurons. , 1995, The Journal of physiology.

[35]  P. Schwindt,et al.  Modal gating of Na+ channels as a mechanism of persistent Na+ current in pyramidal neurons from rat and cat sensorimotor cortex , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[36]  W. Crill,et al.  Persistent sodium current in mammalian central neurons. , 1996, Annual review of physiology.

[37]  V. Crunelli,et al.  Computer simulation of the pacemaker oscillations of thalamocortical cells. , 1992, Neuroreport.

[38]  Stephen R. Williams,et al.  Morphology and membrane properties of neurones in the cat ventrobasal thalamus in Vitro , 1997, The Journal of physiology.

[39]  T. Sejnowski,et al.  A model for 8-10 Hz spindling in interconnected thalamic relay and reticularis neurons. , 1993, Biophysical journal.

[40]  Stephen R. Williams,et al.  On the nature of anomalous rectification in thalamocortical neurones of the cat ventrobasal thalamus in vitro , 1997, The Journal of physiology.

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

[42]  H. Pape Specific bradycardic agents block the hyperpolarization-activated cation current in central neurons , 1994, Neuroscience.

[43]  The theoretical basis for non-exponential time-course of the recovery from inactivation of hodgkin-huxley-type ionic currents , 1996, Neuroscience.

[44]  I. Raman,et al.  Resurgent Sodium Current and Action Potential Formation in Dissociated Cerebellar Purkinje Neurons , 1997, The Journal of Neuroscience.

[45]  W. Vogel,et al.  Single voltage‐activated Na+ and K+ channels in the somata of rat motoneurones. , 1995, The Journal of physiology.

[46]  B. Sakmann,et al.  Amplification of EPSPs by axosomatic sodium channels in neocortical pyramidal neurons , 1995, Neuron.

[47]  V. Crunelli,et al.  A numerical procedure to estimate kinetic and steady-state characteristics of inactivating ionic currents , 1995, Journal of Neuroscience Methods.

[48]  C. January,et al.  Direct measurement of L-type Ca2+ window current in heart cells. , 1992, Circulation research.

[49]  W. Guido,et al.  Burst responses in thalamic relay cells of the awake behaving cat. , 1995, Journal of neurophysiology.

[50]  D. McCormick,et al.  Sleep and arousal: thalamocortical mechanisms. , 1997, Annual review of neuroscience.

[51]  R. Lipowsky,et al.  Dendritic Na+ channels amplify EPSPs in hippocampal CA1 pyramidal cells. , 1996, Journal of neurophysiology.

[52]  M. Gutnick,et al.  Kinetics of slow inactivation of persistent sodium current in layer V neurons of mouse neocortical slices. , 1996, Journal of neurophysiology.

[53]  R. Traub,et al.  A model of a CA3 hippocampal pyramidal neuron incorporating voltage-clamp data on intrinsic conductances. , 1991, Journal of neurophysiology.

[54]  O Belluzzi,et al.  A five-conductance model of the action potential in the rat sympathetic neurone. , 1991, Progress in biophysics and molecular biology.

[55]  M. Gutnick,et al.  Slow inactivation of Na+ current and slow cumulative spike adaptation in mouse and guinea‐pig neocortical neurones in slices. , 1996, The Journal of physiology.

[56]  M. Pirchio,et al.  Postnatal Development of Membrane Properties and δ Oscillations in Thalamocortical Neurons of the Cat Dorsal Lateral Geniculate Nucleus , 1997, The Journal of Neuroscience.

[57]  C.Justin Lee,et al.  Postnatal development of GABAA receptor function in somatosensory thalamus and cortex: whole-cell voltage-clamp recordings in acutely isolated rat neurons , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[58]  D. Prince,et al.  Slow inactivation of a TEA-sensitive K current in acutely isolated rat thalamic relay neurons. , 1991, Journal of neurophysiology.

[59]  A. Morel,et al.  Low-threshold calcium spike bursts in the human thalamus. Common physiopathology for sensory, motor and limbic positive symptoms. , 1996, Brain : a journal of neurology.

[60]  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.

[61]  D. McCormick,et al.  A model of the electrophysiological properties of thalamocortical relay neurons. , 1992, Journal of neurophysiology.

[62]  R. Llinás,et al.  In vitro neurons in mammalian cortical layer 4 exhibit intrinsic oscillatory activity in the 10- to 50-Hz frequency range. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[63]  A. Malafosse Idiopathic generalized epilepsies : clinical, experimental and genetic aspects , 1994 .

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

[65]  Stephen R. Williams,et al.  Electrophysiological and morphological properties of interneurones in the rat dorsal lateral geniculate nucleus in vitro. , 1996, The Journal of physiology.