Mechanisms responsible for calcium signal formation in murine primary sensory neurons: Their impairment by experimentally evoked diabetes

Abstract

Transient increases in Ca²⁺ intracellular concentration (“calcium signals”) evoked by membrane depolarization were studied in primary afferent neurons of the dorsal root ganglia of mice. The mechanisms responsible for the formation of these signals in the cells of large diameter (30–45 µm) were shown to be fundamentally different from those in the cells of small diameter (18–25 µm). The cells of large diameter were characterized by fast recovery of initial [Ca²⁺] _in after the membrane repolarization, which was markedly slowed down by the thapsigargin-induced block of Ca²⁺-ATPase in endoplasmic reticulum. In the cells of small diameter, which are involved mainly in nociceptive signalling, the restoration of the initial [Ca²⁺] _in level was slowed down and was not changed by thapsigargin. It was concluded that in the small neurons, in contrast to the large ones, Ca²⁺ uptake by endoplasmic reticulum is not involved in calcium signal formation; the signals are terminated mainly due to the extrusion of these ions from a cell by plasmalemmal Ca²⁺-ATPase. It was found that both in the animals with streptozotocin-induced diabetes and in the animals with genetically conditioned diabetes the kinetics of calcium signals are selectively impaired. The impairment is characterized by some acceleration of “fast” component and by slowing down of residual [Ca²⁺] _in increase, observed only in the neurons of small diameter. The results suggest that the impairments are due to the changes in the activity of plasmalemmal Ca²⁺-ATPase and in Ca²⁺ uptake by mitochondria, and may be one of the factors causing diabetic neuropathies.