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The Journal of Neuroscience, January 1, 2000, 20(1):76-80

Distinction among Neuronal Subtypes of Voltage-Activated Sodium Channels by µ-Conotoxin PIIIA

Patrick Safo¹, Tamara Rosenbaum¹, Anatoly Shcherbatko¹, Deog-Young Choi¹, Edward Han¹, Juan J. Toledo-Aral³, Baldomero M. Olivera⁴, Paul Brehm¹, and Gail Mandel²

¹ Department of Neurobiology and Behavior and ² Howard Hughes Medical Institute, State University of New York at Stony Brook, Stony Brook, New York 11794, ³ Department of Physiology and Biophysics, School of Medicine, University of Seville, 41009 Seville, Spain, and ⁴ Department of Biology, University of Utah, Salt Lake City, Utah 84112

The functional properties of most sodium channels are too similar to permit identification of specific sodium channel types underlying macroscopic current. Such discrimination would be particularly advantageous in the nervous system in which different sodium channel family isoforms are coexpressed in the same cell. To test whether members of the µ-conotoxin family can discriminate among known neuronal sodium channel types, we examined six toxins for their ability to block different types of heterologously expressed sodium channels. PIIIA µ-conotoxin blocked rat brain type II/IIA (rBII/IIA) and skeletal muscle sodium current at concentrations that resulted in only slight inhibition of rat peripheral nerve (rPN1) sodium current. Recordings from variant lines of PC12 cells, which selectively express either rBII/IIA or rPN1 channel subtypes, verified that the differential block by PIIIA also applied to native sodium current. The sensitivity to block by PIIIA toxin was then used to discriminate between rBII/IIA and rPN1 sodium currents in NGF-treated PC12 cells in which both mRNAs are induced. During the first 24 hr of NGF-treatment, PN1 sodium channels accounted for over 90% of the sodium current. However, over the ensuing 48 hr period, a sharp rise in the proportion of rBII/IIA sodium current occurred, confirming the idea, based on previous mRNA measurements, that two distinct sodium channel types appear sequentially during neuronal differentiation of PC12 cells.

Key words: PC12 cells; ion channel; sodium current; growth factor; CNS; PNS

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Copyright © 2000 Society for Neuroscience  0270-6474/0/20176-05$05.00/0

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