The sodium channel Nav1.5a is the predominant isoform expressed in adult mouse dorsal root ganglia and exhibits distinct inactivation properties from the full-length Nav1.5 channel.
Nav1.5 is the principal voltage-gated sodium channel expressed in heart, and is also expressed at lower abundance in embryonic dorsal root ganglia (DRG) with little or no expression reported postnatally. We report here the expression of Nav1.5 mRNA isoforms in adult mouse and rat DRG. The major isoform of mouse DRG is Nav1.5a, which encodes a protein with an IDII/III cytoplasmic loop reduced by 53 amino acids. Western blot analysis of adult mouse DRG membrane proteins confirmed the expression of Nav1.5 protein. The Na+ current produced by the Nav1.5a isoform has a voltage-dependent inactivation significantly shifted to more negative potentials (by approximately 5 mV) compared to the full-length Nav1.5 when expressed in the DRG neuroblastoma cell line ND7/23. These results imply that the alternatively spliced exon 18 of Nav1.5 plays a role in channel inactivation and that Nav1.5a is likely to make a significant contribution to adult DRG neuronal function.
Kerr
Niall C H
NC
Department of Pharmacology, South Bristol, School of Medical Sciences, University of Bristol, Bristol, BS8 1TD, UK.
Gao
Zhan
Z
Holmes
Fiona E
FE
Hobson
Sally-Ann
SA
Hancox
Jules C
JC
Wynick
David
D
James
Andrew F
AF
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D045744:Cell Line, Tumor; D005727:Ganglia, Spinal / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009447:Neuroblastoma; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014162:Transfection / Q000379:methods
D062554:NAV1.5 Voltage-Gated Sodium Channel; D020033:Protein Isoforms; D012333:RNA, Messenger; C568321:Scn5a protein, mouse; C568322:Scn5a protein, rat; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin