Effect of chronic renal failure on Ca2+ ATPase of brain synaptosomes.

Chronic renal failure (CRF) is associated with a sustained rise in the concentration of cytosolic calcium [( Ca2+]i) of brain synaptosomes. This was attributed to secondary hyperparathyroidism where the excess blood levels of parathyroid hormone (PTH) augment calcium entry into synaptosomes. However, for such an effect of PTH to cause a sustained rise in [Ca2+]i, calcium extrusion out of synaptosomes should be impaired. The study presented here examined the effect of CRF with and without (CRF-PTX) excess PTH and the treatment of CRF rats with verapamil (V) on the Vmax and Km for calcium of synaptosomal Ca2+ ATPase, an enzyme that plays an important role in pumping calcium out of the synaptosomes. The Vmax of synaptosomal Ca2+ ATPase in CRF rats was significantly (P less than 0.01) lower than that of normal, CRF-PTX, CRF-V, and normal-V rats. However, the values in CRF-V were still below normal (P less than 0.05). There were no significant differences in the Km for calcium of synaptosomal Ca2+ ATPase among the five groups of animals. [Ca2+]i was significantly (P less than 0.01) higher in synaptosomes of CRF rats than in normal, CRF-PTX, CRF-V, and normal-V animals, and the values among the latter four groups were not different. The data demonstrate that the activity of synaptosomal Ca2+ ATPase is reduced in CRF rats, and this derangement is related to the excess PTH. This derangement in Ca2+ ATPase activity plays an important role in the genesis of the sustained elevation of synaptosomal [Ca2+]i in CRF.