Abstract
Excitatory neurotransmission in the central nervous system is primarily mediated through the activation of ionotropic glutamate receptors (iGluRs). Among iGluRs, N-methyl-D-aspartate receptors (NMDARs) are unique in their ability to pass large Ca2+ currents, which are essential to the normal physiology and development of excitatory synapses. Classically, the content of Ca2+ current passed by NMDARs has been viewed as a static property of the receptor. However, recent evidence shows that extracellular protons, which are strong negative allosteric modulators of NMDA receptors, are capable of also modulating the receptors' relative Ca2+ permeability, suggesting that NMDAR Ca2+ permeability is under dynamic regulation.
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