In addition to contributing to electrical current that flows across the membranes of neurons when they fire, the divalent cation Ca2+ plays other important roles. Entering through the ionotropic N-methyl-D-aspartate (NMDA receptor), Ca2+ activates signal transduction networks involved in synaptic remodeling and plasticity. Using a battery of modern neurophysiologic approaches, Suzanne Zukin and collaborators from Albert Einstein College of Medicine in New York delved far into the regulation of these NMDA receptors, focusing on their regulation by protein kinase A (PKA) and cyclic AMP (cAMP).1 F1000 faculty member, James Bibb of the University of Texas Southwestern Medical Center, says that "no one has gotten down into the details as this group has."
"By focusing very specifically on what PKA is doing and by using clever and modern techniques - whole cell neurophysiology, molecular biology, calcium imaging - they were able to say that the way PKA regulates receptors is by selectively changing the permeability of the channels to calcium.
"When they inhibited PKA, they reduced the permeability and that reduced calcium-dependent signaling pathways. That's very clever and it's important, because in the very last part of the study, they show that that regulation is probably critical to synaptic plasticity."1. V.A. Skeberdis et al., "Protein kinase A regulates calcium permeability of NMDA receptors," Nat Neurosci, 9:501-10, April 2006.