Biochemical and Biophysical Research Communications
Altered expression and function of sodium channels in large DRG neurons and myelinated A-fibers in early diabetic neuropathy in the rat
Section snippets
Materials and methods
Experimental animals. Male Sprague–Dawley rats were housed in the animal facility of the University of Michigan Unit for Laboratory Animal Medicine, which was maintained at 22 °C, 55% relative humidity, with an automatic 12 h light/dark cycle. The animals received a standard laboratory diet and tap water ad libitum. All experiments were approved by the University of Michigan Committee on Use and Care of Animals according to National Institutes of Health Guidelines.
Induction of diabetes. Diabetes
Large-soma DRG neurons from diabetic rats demonstrated altered amplitude and activation kinetics of sodium currents
Using established criteria [17], we recorded sodium currents in DRG neurons with large soma to evaluate potential changes in sodium current (INa) in this population of neurons in short-term diabetes. Total INa was recorded in large DRG neurons (Cm > 70 pF) using a series of depolarizing voltage commands with a prepulse to −120 mV for 500 ms from a holding potential of −80 mV. The amplitudes of total INa at the rising phase were significantly increased in neurons from diabetic rats compared with the
Discussion
Distinct subtypes of voltage-gated sodium channels appear to play pivotal roles in pain sensation under physiologic and pathophysiologic conditions [10], [19]. In the present study, we report for the first time that large A-fiber DRG neurons demonstrated alterations in the functional properties of TTX-S INa and TTX-R Nav1.9 INa, and in the levels of sodium channel immunoreactivity in the streptozotocin-induced model of diabetic neuropathy. Total INa, TTX-S INa, and ramp current were
Acknowledgments
We thank Dr. Lori L. Isom for valuable discussion and generous gift of the sodium channel antibodies. This work was supported by Grant R01DK056997 to JWW from National Institute of Health and by Pilot/Feasibility study grant from Michigan Diabetes Research and Training Center to SH.
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2019, Clinical NeurophysiologyCitation Excerpt :Mathematical modelling of the excitability data in the T2DM cohort were consistent with previous studies of specific nodal and internodal ion channels in clinical and experimental T2DM (Table 4). The pattern of a decrease in Na+ permeability and increase in the percentage of persistent Na+ has been observed in human and animal studies (Brismar et al., 1987; Hong and Wiley, 2006; Krishnan and Kiernan, 2005; Misawa et al., 2009). Peripheral nerve biopsies from neuropathic T2DM patients and T2DM animal models have also demonstrated there is diffuse redistribution of fast K+ channels from their juxtaparanodal position, which may explain the increase in permeability of these channels in both compartments of the axon (Zenker et al., 2012).