The Journal of Neurophysiology Vol. 78 No. 4 October 1997, pp. 1811-1825
Copyright ©1997 The American Physiological Society

Cellular Mechanisms Underlying Spontaneous Firing in Rat Suprachiasmatic Nucleus: Involvement of a Slowly Inactivating Component of Sodium Current

C.M.A. Pennartz, M. A. Bierlaagh, and A.M.S. Geurtsen

Graduate School Neurosciences Amsterdam, Netherlands Institute for Brain Research, 1105 AZ Amsterdam, The Netherlands

Pennartz, C.M.A., M. A. Bierlaagh, and A.M.S. Geurtsen. Cellular mechanisms underlying spontaneous firing in rat suprachiasmatic nucleus: involvement of a slowly inactivating component of sodium current. J. Neurophysiol. 78: 1811-1825, 1997. Neurons constituting the pacemaker of circadian rhythms, located in the suprachiasmatic nucleus, generate spontaneous firing patterns that change across the day-night cycle. Their average spontaneous firing rate is considered an important functional marker of clock activity because it is highest during daytime and low at night. In this study we investigate the ionic mechanisms underlying spontaneous firing in acutely prepared slices and dissociated neurons of the suprachiasmatic nucleus. In current-clamp mode, spontaneous action potentials were consistently preceded by depolarizing ramps. These ramps were Na⁺ dependent, were sensitive to tetrodotoxin (TTX), and disappeared on hyperpolarization. Ramps and associated spikes were not abolished by blockers of the H current (1 mM cesium) or calcium currents (50 µM nickel or 200 µM cadmium). In voltage-clamped neurons in slices or dissociated neurons, TTX-sensitive and Na⁺-dependent inward current was observed to activate well below firing threshold (60 to 50 mV). The low-threshold component of Na⁺ current inactivated slowly as compared with the fast component that mediates action potentials. However, its inactivation proceeded more rapidly than has been reported for the persistent Na⁺ current in cortical structures. Persistent Na⁺ current was generally absent or small in amplitude. The voltage dependence and kinetics of the slowly inactivating component of Na⁺ current are consistent with the hypothesis that it is partially deinactivated during spike afterhyperpolarizations and contributes significantly to subsequent depolarizing ramps. These observations implicate the slowly inactivating component of Na⁺ current in ionic mechanisms governing spontaneous firing in suprachiasmatic nucleus neurons.

This article has been cited by other articles:

				Y. Kovalsky, R. Amir, and M. Devor Simulation in Sensory Neurons Reveals a Key Role for Delayed Na+ Current in Subthreshold Oscillations and Ectopic Discharge: Implications for Neuropathic Pain J Neurophysiol, September 1, 2009; 102(3): 1430 - 1442. [Abstract] [Full Text] [PDF]

				M. D\#8217;Ascenzo, M. V. Podda, T. Fellin, G. B. Azzena, P. Haydon, and C. Grassi Activation of mGluR5 induces spike afterdepolarization and enhanced excitability in medium spiny neurons of the nucleus accumbens by modulating persistent Na+ currents J. Physiol., July 1, 2009; 587(13): 3233 - 3250. [Abstract] [Full Text] [PDF]

				J. N. Mercer, C. S. Chan, T. Tkatch, J. Held, and D. J. Surmeier Nav1.6 Sodium Channels Are Critical to Pacemaking and Fast Spiking in Globus Pallidus Neurons J. Neurosci., December 5, 2007; 27(49): 13552 - 13566. [Abstract] [Full Text] [PDF]

				C. A. Goddard, E. I. Knudsen, and J. R. Huguenard Intrinsic Excitability of Cholinergic Neurons in the Rat Parabigeminal Nucleus J Neurophysiol, December 1, 2007; 98(6): 3486 - 3493. [Abstract] [Full Text] [PDF]

				Choon Kiat Sim and D. B. Forger Modeling the Electrophysiology of Suprachiasmatic Nucleus Neurons J Biol Rhythms, October 1, 2007; 22(5): 445 - 453. [Abstract] [PDF]

				D. J. Margolis and P. B. Detwiler Different Mechanisms Generate Maintained Activity in ON and OFF Retinal Ganglion Cells J. Neurosci., May 30, 2007; 27(22): 5994 - 6005. [Abstract] [Full Text] [PDF]

				M. Puopolo, E. Raviola, and B. P. Bean Roles of Subthreshold Calcium Current and Sodium Current in Spontaneous Firing of Mouse Midbrain Dopamine Neurons J. Neurosci., January 17, 2007; 27(3): 645 - 656. [Abstract] [Full Text] [PDF]

				S. J. Kuhlman Biological Rhythms Workshop IB: Neurophysiology of SCN Pacemaker Function Cold Spring Harb Symp Quant Biol, January 1, 2007; 72(0): 21 - 33. [Abstract] [PDF]

				L. Forti, E. Cesana, J. Mapelli, and E. D'Angelo Ionic mechanisms of autorhythmic firing in rat cerebellar Golgi cells J. Physiol., August 1, 2006; 574(3): 711 - 729. [Abstract] [Full Text] [PDF]

				A. Enomoto, J. M. Han, C.-F. Hsiao, N. Wu, and S. H. Chandler Participation of sodium currents in burst generation and control of membrane excitability in mesencephalic trigeminal neurons. J. Neurosci., March 29, 2006; 26(13): 3412 - 3422. [Abstract] [Full Text] [PDF]

				M. Puopolo, B. P. Bean, and E. Raviola Spontaneous Activity of Isolated Dopaminergic Periglomerular Cells of the Main Olfactory Bulb J Neurophysiol, November 1, 2005; 94(5): 3618 - 3627. [Abstract] [Full Text] [PDF]

				N. Wu, A. Enomoto, S. Tanaka, C.-F. Hsiao, D. Q. Nykamp, E. Izhikevich, and S. H. Chandler Persistent Sodium Currents in Mesencephalic V Neurons Participate in Burst Generation and Control of Membrane Excitability J Neurophysiol, May 1, 2005; 93(5): 2710 - 2722. [Abstract] [Full Text] [PDF]

				Y. Zhao and J. A Boulant Temperature effects on neuronal membrane potentials and inward currents in rat hypothalamic tissue slices J. Physiol., April 1, 2005; 564(1): 245 - 257. [Abstract] [Full Text] [PDF]

				M. Mantegazza, F. H. Yu, A. J. Powell, J. J. Clare, W. A. Catterall, and T. Scheuer Molecular Determinants for Modulation of Persistent Sodium Current by G-Protein {beta}{gamma} Subunits J. Neurosci., March 30, 2005; 25(13): 3341 - 3349. [Abstract] [Full Text] [PDF]

				M. Hausser, I. M. Raman, T. Otis, S. L. Smith, A. Nelson, S. du Lac, Y. Loewenstein, S. Mahon, C. Pennartz, I. Cohen, et al. The Beat Goes On: Spontaneous Firing in Mammalian Neuronal Microcircuits J. Neurosci., October 20, 2004; 24(42): 9215 - 9219. [Full Text] [PDF]

				A. C. Jackson, G. L. Yao, and B. P. Bean Mechanism of Spontaneous Firing in Dorsomedial Suprachiasmatic Nucleus Neurons J. Neurosci., September 15, 2004; 24(37): 7985 - 7998. [Abstract] [Full Text] [PDF]

				Z. Liu, W. Song, and K. Dong Persistent tetrodotoxin-sensitive sodium current resulting from U-to-C RNA editing of an insect sodium channel PNAS, August 10, 2004; 101(32): 11862 - 11867. [Abstract] [Full Text] [PDF]

				N. I. Kononenko, L.-R. Shao, and F. E. Dudek Riluzole-Sensitive Slowly Inactivating Sodium Current in Rat Suprachiasmatic Nucleus Neurons J Neurophysiol, February 1, 2004; 91(2): 710 - 718. [Abstract] [Full Text] [PDF]

				I. A. Rybak, K. Ptak, N. A. Shevtsova, and D. R. McCrimmon Sodium Currents in Neurons From the Rostroventrolateral Medulla of the Rat J Neurophysiol, September 1, 2003; 90(3): 1635 - 1642. [Abstract] [Full Text] [PDF]

				R. K. Cloues and W. A. Sather Afterhyperpolarization Regulates Firing Rate in Neurons of the Suprachiasmatic Nucleus J. Neurosci., March 1, 2003; 23(5): 1593 - 1604. [Abstract] [Full Text] [PDF]

				M. de Jeu, A. Geurtsen, and C. Pennartz A Ba2+-Sensitive K+ Current Contributes to the Resting Membrane Potential of Neurons in Rat Suprachiasmatic Nucleus J Neurophysiol, August 1, 2002; 88(2): 869 - 878. [Abstract] [Full Text] [PDF]

				M. De Jeu and C. Pennartz Circadian Modulation of GABA Function in the Rat Suprachiasmatic Nucleus: Excitatory Effects During the Night Phase J Neurophysiol, February 1, 2002; 87(2): 834 - 844. [Abstract] [Full Text] [PDF]

				F. Rugiero, M. Gola, W. A A Kunze, J.-C. Reynaud, J. B Furness, and N. Clerc Analysis of whole-cell currents by patch clamp of guinea-pig myenteric neurones in intact ganglia J. Physiol., January 15, 2002; 538(2): 447 - 463. [Abstract] [Full Text] [PDF]

				P. W. Burgoon and J. A. Boulant Temperature-sensitive properties of rat suprachiasmatic nucleus neurons Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2001; 281(3): R706 - R715. [Abstract] [Full Text] [PDF]

				S. G. Waxman Acquired channelopathies in nerve injury and MS Neurology, June 26, 2001; 56(12): 1621 - 1627. [Abstract] [Full Text] [PDF]

				C. M A Pennartz, R. Hamstra, and A. M S Geurtsen Enhanced NMDA receptor activity in retinal inputs to the rat suprachiasmatic nucleus during the subjective night J. Physiol., April 1, 2001; 532(1): 181 - 194. [Abstract] [Full Text] [PDF]

				I. M. Raman, A. E. Gustafson, and D. Padgett Ionic Currents and Spontaneous Firing in Neurons Isolated from the Cerebellar Nuclei J. Neurosci., December 15, 2000; 20(24): 9004 - 9016. [Abstract] [Full Text] [PDF]

				B. D. Bennett, J. C. Callaway, and C. J. Wilson Intrinsic Membrane Properties Underlying Spontaneous Tonic Firing in Neostriatal Cholinergic Interneurons J. Neurosci., November 15, 2000; 20(22): 8493 - 8503. [Abstract] [Full Text] [PDF]

				C. Beurrier, B. Bioulac, and C. Hammond Slowly Inactivating Sodium Current (INaP) Underlies Single-Spike Activity in Rat Subthalamic Neurons J Neurophysiol, April 1, 2000; 83(4): 1951 - 1957. [Abstract] [Full Text] [PDF]

				N. C Aggelopoulos and H. Meissl Responses of neurones of the rat suprachiasmatic nucleus to retinal illumination under photopic and scotopic conditions J. Physiol., February 15, 2000; 523(1): 211 - 222. [Abstract] [Full Text] [PDF]

				M. D. Bevan and C. J. Wilson Mechanisms Underlying Spontaneous Oscillation and Rhythmic Firing in Rat Subthalamic Neurons J. Neurosci., September 1, 1999; 19(17): 7617 - 7628. [Abstract] [Full Text] [PDF]

				V. K. Gribkoff, R. L. Pieschl, T. A. Wisialowski, W. K. Park, G. J. Strecker, M. T. G. de Jeu, C. M. A. Pennartz, and F. E. Dudek A Reexamination of the Role of GABA in the Mammalian Suprachiasmatic Nucleus J Biol Rhythms, April 1, 1999; 14(2): 126 - 130. [Abstract] [PDF]

				I. M. Raman and B. P. Bean Ionic Currents Underlying Spontaneous Action Potentials in Isolated Cerebellar Purkinje Neurons J. Neurosci., March 1, 1999; 19(5): 1663 - 1674. [Abstract] [Full Text] [PDF]

				M. Tanaka, T. R. Cummins, K. Ishikawa, J. A. Black, Y. Ibata, and S. G. Waxman Molecular and functional remodeling of electrogenic membrane of hypothalamic neurons in response to changes in their input PNAS, February 2, 1999; 96(3): 1088 - 1093. [Abstract] [Full Text] [PDF]

				T. R. Cummins, J. R. Howe, and S. G. Waxman Slow Closed-State Inactivation: A Novel Mechanism Underlying Ramp Currents in Cells Expressing the hNE/PN1 Sodium Channel J. Neurosci., December 1, 1998; 18(23): 9607 - 9619. [Abstract] [Full Text] [PDF]

				C.M.A. Pennartz, N.P.A. Bos, M.T.G. D. Jeu, A.M.S. Geurtsen, M. Mirmiran, A. A. Sluiter, and R. M. Buijs Membrane Properties and Morphology of Vasopressin Neurons in Slices of Rat Suprachiasmatic Nucleus J Neurophysiol, November 1, 1998; 80(5): 2710 - 2717. [Abstract] [Full Text] [PDF]

				A. Feigenspan, S. Gustincich, B. P. Bean, and E. Raviola Spontaneous Activity of Solitary Dopaminergic Cells of the Retina J. Neurosci., September 1, 1998; 18(17): 6776 - 6789. [Abstract] [Full Text] [PDF]

				C M A Pennartz, M T G De Jeu, A M S Geurtsen, A A Sluiter, and M L H J Hermes Electrophysiological and morphological heterogeneity of neurons in slices of rat suprachiasmatic nucleus J. Physiol., February 1, 1998; 506(3): 775 - 793. [Abstract] [Full Text] [PDF]