Annexin II/p11 is up-regulated in Purkinje cells in EAE and MS.
The sensory neuron specific sodium channel Na(v)1.8 is normally detectable at only very low levels within cerebellar Purkinje cells. Annexin II light chain (p11) binds to the amino terminus of Na(v)1.8 and facilitates its functional expression within the cell membrane. We previously demonstrated that expression of Na(v)1.8 is up-regulated in cerebellar Purkinje cells in experimental allergic encephalomyelitis (EAE) and multiple sclerosis (MS). In this study we demonstrate that expression of p11 is significantly up-regulated in Purkinje cells in EAE (71 +/- 9.0% vs 21.3 +/- 4.9% in controls) and in MS(65.5 +/- 1.6% vs 21.8 +/- 6.2% in controls). We also demonstrate a high degree of co-expression of p11 and Na(v)1.8 (84.8 +/- 8.9%). Together with earlier results which show that experimental expression of Na(v)1.8 within Purkinje cells perturbs the temporal pattern of impulse generation in these cells, our results extend the evidence for an acquired channelopathy which interferes with cerebellar function in MS.
Craner
Matthew J
MJ
Department of Neurology and PVA/EPVA Center for Neuroscience Research, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208018, New Haven, CT 06520-8018, USA.
Lo
Albert C
AC
Black
Joel A
JA
Baker
David
D
Newcombe
Jia
J
Cuzner
M Louise
ML
Waxman
Stephen G
SG
D000818:Animals; D017306:Annexin A2 / Q000378:metabolism*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D021122:Protein Subunits; D011689:Purkinje Cells / Q000378:metabolism* / Q000502:physiology; D015222:Sodium Channels / Q000378:metabolism*; D015854:Up-Regulation
D017306:Annexin A2; D021122:Protein Subunits; D015222:Sodium Channels