The absence of resurgent sodium current in mouse spinal neurons

The Scn8a gene encodes a neuronal, voltage-gated sodium channel, which is h ighly 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 mut ant 'motor endplate disease', Nature Genetics 10 (1995) 461-365; K.L. Schal ler, D.M. Krzemien, P.J. Yarowsky, B.K. Krueger, J.H. Caldwell, A novel, ab undant sodium channel expressed in neurons and glia, J. Neurosci. 15 (1995) 3231-3242]. Sodium channels in Purkinje cells produce an unusual, "resurge nt" current when the cells are repolarized to intermediate potentials (-60 to -20 mV) following a strong depolarization that completely inactivates tr ansient sodium current [I.M. Raman, L.K. Sprunger, M.H. Meisler, B.P. Bean, Altered subthreshold sodium currents and disrupted firing patterns in Purk inje neurons of Scn8a mutant mice, Neuron 19 (1997) 881-891; I.M. Raman, B. P. Bean, Resurgent sodium current and action potential formation in dissoci ated 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 re sembling those either of Purkinje cells or of Xenopus oocytes after heterol ogous expression of Scn8a. We found that P10-P14 Purkinje cells exhibited r esurgent 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 1 3 of 16 cells; -1.2 to -2.3 pA/pF in three of 16 cells). Furthermore, unlik e 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 wa s 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 t o total sodium current in both in P10-P14 Purkinje cells (similar to 40%; [ 21]) and cultured P7-P8 spinal motoneurons (similar to 70% [K.D. Garcia, 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 dens ity in spinal motoneurons, J. Neurosci. 18 (1998) 5234-5239]). Thus, the pr esence or absence of resurgent current, and of persistent sodium current, a ppears to depend on cellular factors other than the mere presence of the Sc n8a transcript. (C) 1999 Elsevier Science B.V. All rights reserved.