A minimal model for G protein-mediated synaptic facilitation and depression
R. Bertram, J. Swanson, M. Yousef, Z.-P. Feng, G. W. Zamponi
G protein-coupled receptors are ubiquitous in neurons, as well as other cell types. Activation of receptors by hormones or neurotransmitters splits the G protein heterotrimer into G_alpha and G_beta_gamma subunits. It is now clear that G_beta_gamma directly inhibits calcium channels, putting them into a reluctant state. The effects of G_beta_gamma depend on the specific beta and gamma subunits present, as well as the beta subunit isoform of the N-type calcium channel. We describe a minimal mathematical model for the effects of G protein action on the dynamics of synaptic transmission. The model is calibrated by data obtained by transfecting G protein and calcium channel subunits into tsA-201 cells. We demonstrate with numerical simulations that G protein action can provide a mechanism for either short-term synaptic facilitation or depression, depending on the manner in which G protein-coupled receptors are activated. The G protein action performs high-pass filtering of the presynaptic signal, with a filter cutoff that depends on the combination of G protein and calcium channel subunits present. At stimulus frequencies above the cutoff, trains of single spikes are transmitted, while only doublets are transmitted at frequencies below the cutoff. Finally, we demonstrate that relief of G protein inhibition can contribute to paired-pulse facilitation.