We investigated the prediction of a relationship between the magnitude of activity-dependent increases in postsynaptic calcium and both the magnitude and direction of synaptic plastic change in the central nervous system (Cho et al. 2000, 2001). In the present study we have investigated whether kainate receptors are present on perirhinal cortex neurones and what mechanisms regulate the function of these receptors.

Neurones were cultured from perirhinal cortex of 3-to 5-day-old humanely killed rat pups and fluo-3-AM used to detect changes in calcium, as previously described (Cho et al. 2000). All experiments were conducted in the presence of TTX, picrotoxin, antagonists for NMDA and AMPA receptors, and L-, N-, P- and Q-type voltage-gated calcium channel blockers. All efforts were made to minimise animal suffering in accordance with the UK Animals (Scientific Procedures) Act, 1986. The GluR5 agonist ATPA (5 µM) produced an increase in fluorescence, indicating that GluR5-containing kainate receptors couple directly to an increase in intracellular calcium. Increasing the levels of protein kinase C (with phorbol esters) enhanced the calcium rise due to GluR5 activation. Furthermore, the GluR5-dependent calcium signal was significantly reduced in the presence of a PKC inhibitor (bisindolymaleimide-I HCl). However, neither the PKA activator (forskolin) nor the inhibitor (KT5720) had any effect on the ATPA-induced calcium response. These results suggest that phosphorylation by PKC can regulate the function of GluR5-containing kainate receptors. It will be of interest to test whether glutamate or other receptors that increase PKC can also modulate kainate receptor function.

This work was supported by the BBSRC.

Cho, K., Aggleton, J.P., Brown, M.W. & Bashir, Z.I. (2001). J. Physiol. 532, 459-466. abstract

Cho, K., Kemp, N., Noel, J., Aggleton, J.P., Brown, M.W. & Bashir, Z.I. (2000). Nature Neuroscience 3, 150-156.