Erk1/2 inhibit synaptic vesicle exocytosis through L-type calcium channels.

L-type calcium channels play only a minor role in basal neurotransmitter release in brain neurons but contribute significantly after induction of plasticity. Very little is known about mechanisms that enable L-type calcium channel participation in neurotransmitter release. Here, using mouse primary cortical neurons, we found that inhibition of Erk1/2 (extracellular signal-regulated kinases 1 and 2) enhanced synaptic vesicle exocytosis by increasing calcium influx through L-type calcium channels. Furthermore, inhibition of Erk1/2 increased the surface fraction of these channels. These findings indicate a novel inhibitory effect of Erk1/2 on synaptic transmission through L-type calcium channels.