NMDA receptor channels are nonspecific cation channels that are permeable for sodium, potassium, and calcium ions. The fraction of calcium ions contributing to the total cation current through NMDA receptor channels

is about 6%–12% (Burnashev et al., 1995, Garaschuk et al., 1996, Rogers and Dani, 1995 and Schneggenburger et al., 1993). The specific properties of NMDA receptors are determined by the subunit composition, the phosphorylation status of the receptor, and, importantly, the membrane potential of the neuron. NMDA receptors are heteromers of the subunit NR1 in combination with NR2 subunits, like NR2A or NR2B CX-5461 cost (Bloodgood and Sabatini, 2007a). In CA1 hippocampal neurons, dendritic spines express preferentially either the NR2A or the NR2B subunits and, in a given neuron, the contribution of NR2A- or click here NR2B-mediated calcium influx to the spine calcium signal is variable among the different dendritic spines (Sobczyk et al., 2005). Another factor

that determines the permeability for calcium ions is the phosphorylation status of the NMDA receptors. Thus, the permeability is enhanced by increased phosphorylation whereas dephosphorylation decreases calcium permeability (Skeberdis et al., 2006 and Sobczyk and Svoboda, 2007). Finally, a critical modulator of NMDA receptor function is the membrane potential 3-mercaptopyruvate sulfurtransferase as it determines the efficacy of the voltage-dependent block of NMDA receptors by magnesium

(Mayer et al., 1984 and Nowak et al., 1984). The NMDA receptor-dependent ionic current increases as a function of increasing neuronal depolarization from the resting membrane potential. Calcium-permeable AMPA receptors are another class of ionotropic glutamate receptors. They are found in many forms of aspiny GABAergic neurons and characterized by the relative lack of the GluR2 receptor subunit (Jonas et al., 1994). GluR2-lacking AMPA receptors are permeable for sodium, calcium, potassium, but also zinc ions (Liu and Zukin, 2007). They exhibit fast gating kinetics (Geiger et al., 1995) and their inwardly rectifying I-V relationship arises from a voltage-dependent block due to intramolecular polyamines (Bowie and Mayer, 1995 and Koh et al., 1995). The subunit composition varies in a synapse-specific manner within individual neurons (Tóth and McBain, 1998). This feature enables individual neurons to produce different types of responses to distinct synaptic inputs. Importantly, the presence of GluR2-containing and GluR2-lacking AMPA receptors is not static, but is highly regulated, particularly in response to neuronal activity (Liu and Cull-Candy, 2000). Thus, permeability of AMPA receptors to calcium is dynamic within a given neuron and can therefore contribute to synaptic plasticity mechanisms in aspiny neurons.