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

E. Kostyuk, N. Voitenko, I. Kruglikov, A. Shmigol, V. Shishkin, A. Efimov, P. Kostyuk

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

Aims/hypothesis. Distal neuropathy is the most common complication of diabetes 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 used. Changes in intracellular free calcium concentrations ([Ca2+]i) were measured fluorometrically in primary nociceptive neurons from dorsal root ganglia and in secondary nociceptive neurons from substantia gelatinosa of spinal dorsal horn slices. Results. Measurements of [Ca2+]i increases induced in dorsal root ganglion and dorsal horn neurons by membrane depolarization did not show any substantial 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 ganglion and dorsal horn neurons induced a transient elevation of [Ca2+]i which was less prominent in cells from diabetic animals. Short-term application of a calcium channel blocker nifedipine showed a substantial amplification of its action in diabetic neurons. However, chronic administration of nimodipine induced a clear increase in the peak values of transients in dorsal root ganglion neurons of diabetic animals compared with those of untreated animals. Conclusion/interpretation. The described changes of calcium signalling in nociceptive neurons could be the reason for the development of distal polyneuropathy and its symptoms in the early stages of diabetes mellitus.

Original languageEnglish
Pages (from-to)1302-1309
Number of pages8
JournalDiabetologia
Volume44
Issue number10
DOIs
Publication statusPublished - 2001
Externally publishedYes

Keywords

  • Calcium channels
  • Diabetes mellitus
  • Dihydropyridines
  • Neurons
  • Ryanodine receptor calcium release channel
  • Spinal cord
  • Streptozotocin

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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