Compensatory increase in P/Q-calcium current-mediated synaptic transmission following chronic block of N-type channels

Synaptic transmission is triggered by presynaptic calcium influx through voltage-gated calcium channels. Axon terminals of central neurons express a diverse set of homologous calcium channels, giving rise to P/Q-, N-, and R-type calcium currents. The relative contribution of these components to presynaptic calcium signalling is heterogeneous and incompletely understood. Here we report that chronic block of N-type calcium channels in developing cultured rat hippocampal neurons leads to a compensatory up-regulation of P/Q-type calcium currents. This increase was measured directly by recording whole-cell calcium currents as well as in spontaneous inhibitory postsynaptic currents, indicating a global functional up-regulation of the P/Q-component. In contrast, immunocytochemical stainings as well as quantitative real-time PCR analysis did not reveal an increased expression of Cav 2.1, the underlying calcium channel α-subunit. We conclude that developing hippocampal neurons can compensate for the loss of one calcium current component by up-regulation of alternative isoforms at the post-translational level.