Changes in calcium signalling in dorsal horn neurons in rats with streptozotocin-induced diabetes

Abstract

Intracellular calcium signalling was studied in the dorsal horn from neurons of rats with streptozotocin-induced diabetes versus control animals. The cytoplasmic Ca 2+ concentration ([Ca 2+] i) was measured in Fura-2 acetoxymethyl ester-loaded dorsal horn neurons from acutely isolated spinal cord slices using a fluorescence technique. The recovery of depolarization-induced [Ca 2+] i increase was delayed in diabetic neurons compared with normal animals. In normal neurons, [Ca 2+] i after the end of KCl depolarization recovered to the basal level monoexponentially with a time constant of 8.0±0.5 s ( n=23), while diabetic neurons showed two exponentials in the [Ca 2+] i recovery. The time constants of these exponentials were 7.2±0.5 and 23.0±0.6 s ( n=19), respectively. The amplitude of calcium release from caffeine-sensitive endoplasmic reticulum calcium stores became significantly smaller in diabetic neurons. The amplitudes of [Ca 2+] i transients evoked by 30 mM caffeine were 268±29 nM ( n=13) and 31±9 nM ( n=17) in control and diabetic neurons, respectively. We conclude that streptozotocin-induced diabetes is associated with prominent changes in the mechanisms responsible for [Ca 2+] i regulation, which presumably include a slowdown of Ca 2+ elimination from the cytoplasm by the endoplasmic reticulum.