9744935

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3

We examined the hypothesis that exposure of nondiabetic rat dorsal root ganglion (DRG) neurons to sera from diabetic BB/W rats would produce an increase in calcium currents associated with impaired regulation of the inhibitory G protein-calcium channel complex. Acutely dissociated rat DRGs were incubated for 18-24 h in medium supplemented with sera (10% vol/vol) from either diabetic rats with neuropathy or age-matched, nondiabetic controls. Exposure of DRG neurons to sera from diabetic BB/W rats resulted in a surface membrane immunofluorescence pattern when treated with an anti-rat light-chain antibody that was not observed in neurons exposed to control sera. Calcium current density (IDCa) was assessed with the use of the whole cell variation of the patch-clamp technique. IDCa in neurons exposed to diabetic sera was significantly increased compared with neurons exposed to control sera. Guanine nucleotide-binding (G) protein regulation of calcium channel function was examined with the use of a two-pulse "facilitation" or IDCa enhancement protocol in the presence of activators [guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S)] or antagonists [guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) and pertussis toxin (PTX)] of G protein function. Facilitation was significantly decreased in neurons exposed to diabetic sera. Intracellular diffusion of neurons with GDP beta s blocked facilitation, whereas dialysis with GTP gamma s increased facilitation to a similar magnitude in neurons exposed to either diabetic or control sera. Treatment with PTX resulted in a significant increase in IDCa and approximately 50% decrease in facilitation in neurons treated with control sera but no significant changes in neurons exposed to diabetic sera. We conclude that serum from diabetic BB/W rats with neuropathy contains an autoimmune immunoglobulin that impairs regulation of the inhibitory G protein-calcium channel complex, resulting in enhanced calcium influx. Regulation of the inhibitory G protein-calcium channel complex involves PTX-sensitive and -insensitive G proteins.

eng

IM

MEDLINE

0022-3077

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NLM

1236-44

pubmed-meshheading:9744935-Animals, pubmed-meshheading:9744935-Autoantibodies, pubmed-meshheading:9744935-Autoantigens, pubmed-meshheading:9744935-Calcium, pubmed-meshheading:9744935-Calcium Channels, pubmed-meshheading:9744935-Diabetes Mellitus, Type 1, pubmed-meshheading:9744935-GTP-Binding Proteins, pubmed-meshheading:9744935-Ganglia, Spinal, pubmed-meshheading:9744935-Guanosine 5'-O-(3-Thiotriphosphate), pubmed-meshheading:9744935-Guanosine Diphosphate, pubmed-meshheading:9744935-Membrane Potentials, pubmed-meshheading:9744935-Neuroimmunomodulation, pubmed-meshheading:9744935-Neurons, Afferent, pubmed-meshheading:9744935-Patch-Clamp Techniques, pubmed-meshheading:9744935-Pertussis Toxin, pubmed-meshheading:9744935-Rats, pubmed-meshheading:9744935-Rats, Inbred BB, pubmed-meshheading:9744935-Rats, Sprague-Dawley, pubmed-meshheading:9744935-Thionucleotides, pubmed-meshheading:9744935-Virulence Factors, Bordetella

Serum from diabetic BB/W rats enhances calcium currents in primary sensory neurons.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't