A model for a G-protein-mediated mechanism for synaptic channel modulation Gabriel Soto * , Hans G. Othmer School of Mathematics, University of Minnesota, Minneapolis, MN 55455, United States Received 23 May 2005; received in revised form 9 December 2005; accepted 13 January 2006 Available online 15 March 2006 Abstract Neurons communicate with other neurons via specialized structures called synapses, at which the digital voltage signal encoded in an action potential is converted into an analog chemical signal. An action poten- tial that arrives at the presynaptic face triggers release of neurotransmitter from vesicles in a calcium-depen- dent manner, and the neurotransmitter diffuses across the synaptic cleft and binds to receptors on the post-synaptic face, where it may trigger a postsynaptic action potential. Calcium is a critical component of the release process, and its spatio-temporal dynamics can control the release and can lead to facilitation or augmentation. However, how cells regulate cytoplasmic calcium so that exocytosis can be triggered suc- cessfully is still not completely understood. We propose a mechanism, based upon the experimental findings of Barrett and Rittenhouse [C.F. Barrett, A.R. Rittenhouse, Modulation of N-type calcium channel activity by G-proteins and protein kinase C, J. Gen. Physiol. 115 (3) (2000) 277], for the regulation of calcium influx through N-type channels in the presynaptic terminal by PKC and downstream effectors of G-protein acti- vation. This proposed modulatory mechanism consists of a feedback loop involving cytoplasmic calcium, neurotransmitters and G-protein-coupled receptors. We study the dynamics of each component separately and then we address how kinetic properties of the components and the frequency of the stimuli affect the regulatory mechanisms presented here. Ó 2006 Elsevier Inc. All rights reserved. 0025-5564/$ - see front matter Ó 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.mbs.2006.01.005 * Corresponding author. Present address: Center for BioDynamics, Boston University, 111 Cummington Street, Boston, MA 02115, United States. Tel.: +1 617 353 9543; fax: +1 617 353 4889. E-mail address: gabys@math.bu.edu (G. Soto). www.elsevier.com/locate/mbs Mathematical Biosciences 200 (2006) 188–213