Molecular Brain Research 101 (2002) 126–131 www.elsevier.com / locate / bres Research report Axotomy does not up-regulate expression of sodium channel Na 1.8 v in Purkinje cells a,b, c c a,b * J.A. Black , I. Dusart , C. Sotelo , S.G. Waxman a Department of Neurology and PVA / EPVA Center for Neuroscience Research, Yale University School of Medicine, New Haven, CT 06510, USA b Rehabilitation Research Center, VA Connecticut Healthcare System, West Haven, CT 06516, USA c Institut National de la Sante et de la Recherche Medicale U106, Hopital de la Salpetriere, 75651 Paris cedex, 13, France Accepted 8 February 2002 Abstract Aberrant expression of the sensory neuron specific (SNS) sodium channel Na 1.8 has been demonstrated in cerebellar Purkinje cells in v experimental models of multiple sclerosis (MS) and in human MS. The aberrant expression of Na 1.8, which is normally present in v primary sensory neurons but not in the CNS, may perturb cerebellar function, but the mechanisms that trigger it are not understood. Because axotomy can provoke changes in Na 1.8 expression in dorsal root ganglion (DRG) neurons, we tested the hypothesis that v axotomy can provoke an up-regulation of Na 1.8 expression in Purkinje cells, using a surgical model that transects axons of Purkinje cells v in lobules IIIb–VII in the rat. In situ hybridization and immunocytochemistry did not reveal an up-regulation of Na 1.8 mRNA or protein v in axotomized Purkinje cells. Hybridization and immunostaining signals for the sodium channel Na 1.6 were clearly present, v demonstrating that sodium channel transcripts and protein were present in experimental cerebella. These results demonstrate that axotomy does not trigger the expression of Na 1.8 in Purkinje cells.  2002 Elsevier Science B.V. All rights reserved. v Theme: Excitable membranes and synaptic transmission Topic: Sodium channels Keywords: Axotomy; Cerebellum; Purkinje cell; Sodium channel Na 1.8 v 1. Introduction discrete subpopulations of neurons in dorsal root ganglia (DRG) and trigeminal ganglia neurons, and is not ex- Although multiple sclerosis (MS) has classically been pressed at significant levels within the CNS [1,39]. considered to be a demyelinating disease, it is now well- The electrogenic properties of neurons, including Pur- established that axonal degeneration occurs in MS kinje cells, depend on the type(s) of sodium channels that [15,23,34,35,45], where it appears to be correlated with they express [27,31,32,36,43,47]. Mutations of the Na 1.6 v non-remitting disability [15,24,33]. Recent data also sug- (NaCh6) sodium channels that are normally present within gest that an acquired channelopathy, characterized by the Purkinje cells perturb cerebellar function, thereby produc- abnormal expression of sensory neuron specific (SNS; ing ataxia [29,37]. The unique physiological signature of Na 1.8) voltage-gated sodium channels in cerebellar Pur- Na 1.8, which includes slow development of inactivation, v v kinje cells, occurs both in genetic and autoimmune models depolarized voltage-dependence of inactivation and rapid of MS [6,7] and in human MS [6]. Sodium channel Na 1.8 recovery from inactivation [1,18,22,39], suggests that v is normally expressed in a highly specific manner within abnormal expression of this channel might have an espe- cially large effect on the pattern of electrogenesis. Con- sistent with this suggestion, in a patch clamp study which *Corresponding author. Present address: Neuroscience Research Center compared DRG neurons from transgenic Na 1.8 knockout v (127A),VA Connecticut, 950 Campbell Avenue, West Haven, CT 06516, [2] and wildtype mice, Renganathan et al. [38] showed that USA. Tel.: 11-203-937-3802; fax:11-203-937-3801. E-mail address: joel.black@yale.edu (J.A. Black). the expression of Na 1.8 channels influences the temporal v 0169-328X / 02 / $ – see front matter  2002 Elsevier Science B.V. All rights reserved. PII: S0169-328X(02)00200-0