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

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Abstract
Ristic, Helen, Shanthi Srinivasan, Karen E. Hall, Anders A. F. Sima, and John W. Wiley. Serum from diabetic BB/W rats enhances calcium currents in primary sensory neurons. J. Neurophysiol. 80: 1236–1244, 1998. 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 ( I DCa) was assessed with the use of the whole cell variation of the patch-clamp technique. I DCa 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 I DCa enhancement protocol in the presence of activators [guanosine 5′-O-(3-thiotriphosphate) (GTPγS)] or antagonists [guanosine 5′-O-(2-thiodiphosphate) (GDPβS) and pertussis toxin (PTX)] of G protein function. Facilitation was significantly decreased in neurons exposed to diabetic sera. Intracellular diffusion of neurons with GDPβs blocked facilitation, whereas dialysis with GTPγs increased facilitation to a similar magnitude in neurons exposed to either diabetic or control sera. Treatment with PTX resulted in a significant increase in I DCa and ∼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.

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