Differential coupling of N- and P/Q-type calcium channels to glutamate exocytosis in the rat cerebral cortex.

In nerve terminals, the activation of Ca(2+) channels of either the P/Q or N type triggers glutamate release. In turn, presynaptic metabotropic glutamate receptors control this process through the modulation of these Ca(2+) channels. By measuring glutamate release from cerebrocortical nerve terminals we show that at physiological concentrations of extracellular Ca(2+), the agonist L(+)-2-amino-4-phosphonobutyrate only reduced the N-type channel coupled release. However, at lower concentrations of extracellular calcium the contribution of N-type channels was abolished and P/Q-type channels were entirely responsible for the remaining release of glutamate. Under these conditions, L(+)-2-amino-4-phosphonobutyrate was capable of reducing the P/Q-type channel mediated release. These results indicate that N-type Ca(2+) channels are less efficiently coupled to glutamate release than P/Q-type channels and that this differential coupling may have important implications for presynaptic modulation of synaptic transmission.