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Increased expression of a slow Na+ conductance in peripheral nerves in experimental diabetic neuropathy in mice

Introduction: Previous results obtained in this laboratory and elsewhere identified defects in Na and a decrease in potassium (K+) channels activity (in particular IR) in peripheral nerves of diabetic rats. Recently, a novel sodium channel (slow TTX-resistant) has been characterized in peripheral nerves and appears to be modified after a variety of neuronal lesions. In the present study we examined if diabetic state affect these slow sodium channels in peripheral nerves of experimental diabetes in mice. Methods: Compound action potentials (CAP) and delayed depolarization (DD), obtained after application of 4-aminopyrridine, and considered to manifest slow sodium conductance were measured using sucrose gap technique. Experiments were performed on sciatic nerves and dorsal root ganglia (DRG) in mice. Results: DD was found to be extracellular [Na+]-dependent, increasing significantly when [Na+] was doubled. Recovery period of DD was 30 ms compared to 7 ms for CAP (double pulse stimulation) suggesting different kinetics. Normalizing the data by measuring ratio of areas of DD / CAP indicated significant increase in DD in the diabetic animal group. Conclusions: Our results demonstrate that DD represents a slow Na-dependent conductance that is upregulated in diabetic state, unlike its downregulation in nerve injury. This approach is suitable for pharmacological studies of slow Na conductances in neuropathies. Supported by: in part by CDA, ALS & CIHR.

slow sodium conductance; neuropathy; diabetes

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