Estimating the Ca Block of NMDA Receptors with Single-Channel Electrophysiology.

In vertebrate central neurons, NMDA receptors are glutamate- and glycine-gated ion channels that allow the passage of Na and Ca ions into the cell when these neurotransmitters are simultaneously present. The passage of Ca is critical for initiating the cellular processes underlying various forms of synaptic plasticity. These Ca ions can autoregulate the NMDA receptor signal through multiple distinct mechanisms to reduce the total flux of cations. One such mechanism is the ability of Ca ions to exclude the passage of Na ions resulting in a reduced unitary current conductance. In contrast to the well-characterized Mg block, this "channel block" mechanism is voltage-independent. In this chapter, we discuss theoretical and experimental considerations for the study of channel block by Ca using single-channel patch-clamp electrophysiology. We focus on two classic methodologies to quantify the dependence of unitary channel conductance on external concentrations of Ca as the basis for quantifying Ca block.