The absence of resurgent sodium current in mouse spinal neurons.
The Scn8a gene encodes a neuronal, voltage-gated sodium channel, which is highly expressed in both cerebellar Purkinje neurons and spinal motoneurons [D.L. Burgess, D.C. Kohrman, J. Galt, N.W. Plummer, J.M. Jones, B. Spear, M.H. Meisler, Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease', Nature Genetics 10 (1995) 461-465; K.L. Schaller, D.M. Krzemien, P.J. Yarowsky, B.K. Krueger, J.H. Caldwell, A novel, abundant sodium channel expressed in neurons and glia, J. Neurosci. 15 (1995) 3231-3242]. Sodium channels in Purkinje cells produce an unusual, "resurgent" current when the cells are repolarized to intermediate potentials (-60 to -20 mV) following a strong depolarization that completely inactivates transient sodium current [I.M. Raman, L.K. Sprunger, M.H. Meisler, B.P. Bean, Altered subthreshold sodium currents and disrupted firing patterns in Purkinje neurons of Scn8a mutant mice, Neuron 19 (1997) 881-891; I.M. Raman, B.P. Bean, Resurgent sodium current and action potential formation in dissociated cerebellar Purkinje neurons, J. Neurosci. 17 (1997) 4517-4526]. Here, we have examined whether large spinal neurons (predominantly motoneurons), isolated from P6-P8 mice and cultured overnight, produce sodium currents resembling those either of Purkinje cells or of Xenopus oocytes after heterologous expression of Scn8a. We found that P10-P14 Purkinje cells exhibited resurgent current (ranging from -3.6 to -15.4 pA/pF in 16 cells at -40 mV), but cultured spinal neurons had little or no such current (<0.5 pA/pF in 13 of 16 cells; -1.2 to -2.3 pA/pF in three of 16 cells). Furthermore, unlike Scn8a channels heterologously expressed in Xenopus oocytes [M.R. Smith, R.D. Smith, N.W. Plummer, M.H. Meisler, A.L. Goldin, Functional analysis of the mouse Scn8a sodium channel. J. Neurosci. 18 (1998) 6093-6102], there was not a prominent component of persistent sodium current in either Purkinje neurons or large spinal neurons. Based on analysis of cells from mice with a Scn8a null mutation, Scn8a channels appear to contribute significantly to total sodium current in both in P10-P14 Purkinje cells (approximately 40%; [21]) and cultured P7-P8 spinal motoneurons (approximately 70% [K.D. García, L.K. Sprunger, M.H. Meisler, K.G. Beam, The sodium channel Scn8a is the major contributor to the postnatal developmental increase of sodium current density in spinal motoneurons, J. Neurosci. 18 (1998) 5234-5239]). Thus, the presence or absence of resurgent current, and of persistent sodium current, appears to depend on cellular factors other than the mere presence of the Scn8a transcript.
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Department of Anatomy, Colorado State University, Fort Collins, CO, USA.
Beam
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D000200:Action Potentials; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000502:physiology; D051379:Mice; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000166:cytology / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*
D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C491046:Scn8a protein, mouse; D015222:Sodium Channels