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Slow sodium conductance is increased in sciatic nerves from SOD1G37R transgenic mice (amyotrophic lateral sclerosis model) in symptomatic phase.

BACKGROUND: Previous results obtained in this laboratory identified defects in Na and K channels functioning in low threshold myelinated peripheral axons of mice expressing human heavy neurofilaments, a model of amyotrophic lateral sclerosis (ALS) (Kriz et al Exp Neurol 163: 414-421, 2000). OBJECTIVES: To investigate electrophysiological properties of sciatic nerves (SN) from SOD1G37R transgenic mice (another model of ALS) during pre-symptomatic phase (PSP ; 6-9 months of age) and symptomatic phase (SP ; 10 12 m) and compare them with wild type (WT) mice of equivalent age. METHODS: Compound action potential (CAP) evoked in SN and delayed depolarization (DD ; observed after 4-aminopyridine and considered the manifestation of slow sodium conductance(s) in sensory axons) were measured in vitro (22-26 C) using sucrose gap technique. RESULTS: Conduction velocity (CV) was significantly decreased only in SP (18.27 0.47 m/s and 11.42 1.0 m/s for WT and SOD1G37R, respectively, mean S.E., p< 0.001, n=6). Similarly, the area of DD (normalized as DD/CAP area ratio) was significantly increased only in SP (104% 16.4% and 317% 40.6% for WT and SOD1G37R, respectively, mean S.E., p<0.001, n= 6, normalized by DD/CAP ratio of control). There was no difference in refractory period (RP) of CAP between WT and SOD1G37R mice in PSP of ALS but RP was significantly prolonged in SP of transgenic mice. CONCLUSION: These results are compatible with an increase of slow Na conductance (measured as DD) in peripheral axons of SOD1G37Ranimals. This change most likely occurs in large sensory axons ; the degree of increase in motor axons is currently being investigated. The increase in resulting Na influx may have a pathogenetic role in cell damage in SOD1G37R mice. Support Contributed By: in part by ALS and CDA.

amyotrophic lateral sclerosis; SOD1G37R transgenic mice; slow sodium conductance

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