Wächtler J, Mayer C, Rucker F, Grafe P
Department of Physiology, University of Munich, Germany.
Brain Res. 1996 Jun 24;725(1):30-6. doi: 10.1016/0006-8993(96)00320-4.
Peripheral nerves in diabetic patients show an enhanced liability to ischaemic lesions. Using an in vitro model, we have now analysed the possible role of intracellular proton (pHi) and calcium concentrations ([Ca2+]i) for the pathophysiology of this phenomenon. Isolated rat spinal roots were preincubated for 3 to 6 h in either 5 or 25 mM of D-glucose before transient exposure to gaseous hypoxia or cyanide. Intracellular pH and Ca2+ concentrations were measured photometrically by means of the fluorescent dyes carboxy-SNARF-1 and a combination of Calcium Green-1 and Fura Red, respectively. The following observations were made. (a) The presence of 25 mM D-glucose resulted in stronger intracellular acidification and much slower post-hypoxic recovery of pHi as compared to 5 mM D-glucose. (b) Intracellular calcium increased during hypoxia and recovered quickly on reoxygenation. There were no statistically significant differences between the Ca2+ signals in either high or normal concentrations of D-glucose, although on average less rise was seen in high glucose. (c) Inhibition of glycolysis with iodoacetate reduced the acidification but amplified the rise in [Ca2+]i seen during transient hypoxia. These data suggest that hypoxia-induced nerve acidification rather than a rise in [Ca2+]i might contribute to ischaemic lesions found in diabetic neuropathy.
