Effect of angiotensin IV on the acquisition of the water maze task and ryanodine channel function

Abstract

In the present study, we investigated the effect of angiotensin IV (Ang IV) on the acquisition of spatial task by rats, expression and function of ryanodine receptors (RyRs) and on Ca 2+ transport in microsomal membranes isolated from rat hippocampus, the brain structure essential for spatial memory. Wistar rats, injected intracerebroventricularly with 1 nmol of Ang IV or saline were subjected to the water maze training using hidden (learning) or visible (nonlearning) escape platform. Rats showed overall good acquisition of the task and mean escape latency decreased from 55 s to less than 10 s during the 5-day training. Learning significantly increased [ 3H]-ryanodine binding to microsomal RyRs and markedly decreased both receptor affinity constant for the ligand and microsomal Ca 2+ uptake. Ang IV was without effect on the rate of acquisition of the spatial task but increased (by 47%) maximal ryanodine binding in hippocampal microsomes of the trained rats. The peptide, however, did not affect decreased net Ca 2+ uptake in rats subject to learning procedure. Since microsomal Ca 2+-ATPase activity was similar in all tested groups, the lower net Ca 2+ uptake in the trained rats could be attributed to the elevated expression of RyRs and resulting to increased Ca 2+ release.