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
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.