Roles of Calmodulin and a N-Methyl-D-Aspartate Receptor - Pannexin-1 Signaling Complex in Connexin-36 Plasticity

The synergic actions of calcium, calmodulin, and calmodulin kinase II are the central mechanism for synaptic plasticity. Until the last two decades, chemical synapses through N-methyl D-aspartate receptors were thought to be the only synapse that demonstrates plasticity. Our research has shown previously that electrical synapses use CaM/CaMKII interaction in a similar Ca2+-dependent process for plasticity. New evidence suggests that other channels and kinases have modulatory roles in the whole mechanism. This thesis explores the contributions and roles that different kinases, receptors, and channels have on electrical synaptic plasticity. The over-arching hypothesis is that the activation of N-methyl-D-aspartate receptors and pannexin1 channels drives Ca2+ change for physiological signaling of Cx36 plasticity. Here, I introduce a novel modality for CaM electrical synapse regulation and unify the electro-chemical transmission mechanism. I demonstrate that both N-methyl-D-aspartate receptors and pannexin1 channels influence the plasticity at the gap junction nexus. These findings opened up new avenues to expand on mechanisms for synaptic plasticity.