Diabetes-induced changes in calcium homeostasis and the effects of calciumchannel blockers in rat and mice nociceptive neurons

Citation
E. Kostyuk et al., Diabetes-induced changes in calcium homeostasis and the effects of calciumchannel blockers in rat and mice nociceptive neurons, DIABETOLOG, 44(10), 2001, pp. 1302-1309
Citations number
28
Categorie Soggetti
Endocrynology, Metabolism & Nutrition","Endocrinology, Nutrition & Metabolism
Journal title
DIABETOLOGIA
ISSN journal
0012186X → ACNP
Volume
44
Issue
10
Year of publication
2001
Pages
1302 - 1309
Database
ISI
SICI code
0012-186X(200110)44:10<1302:DCICHA>2.0.ZU;2-Z
Abstract
Aims/hypothesis. Distal neuropathy is the most common complication of diabe tes mellitus, making it important to reveal the cellular mechanisms leading to its development, one of which might be the alteration in intracellular calcium homeostasis in primary and secondary nociceptive neurons. We aimed to investigate these possible changes. Methods. Control and streptozotocin-treated diabetic rats and mice were use d. Changes in intracellular free calcium concentrations ([Ca2+](i)) were me asured fluorometrically in primary nociceptive neurons from dorsal root gan glia and in secondary nociceptive neurons from substantia gelatinosa of spi nal dorsal horn slices. Results. Measurements of [Ca2+](i) increases induced in dorsal root ganglio n and dorsal horn neurons by membrane depolarization did not show any subst antial difference in their peak amplitudes in control and diabetic animals. However, a definite prolongation of the decay phase of the transients was observed under diabetic conditions. Caffeine application to dorsal root gan glion and dorsal horn neurons induced a transient elevation of [Ca2+](i) wh ich was less prominent in cells from diabetic animals. Short-term applicati on of a calcium channel blocker nifedipine showed a substantial amplificati on of its action in diabetic neurons. However, chronic administration of ni modipine induced a clear increase in the peak values of transients in dorsa l root ganglion neurons of diabetic animals compared with those of untreate d animals. Conclusion/interpretation. The described changes of calcium signalling in n ociceptive neurons could be the reason for the development of distal polyne uropathy and its symptoms in the early stages of diabetes mellitus.