Theoretical calculation of NMDA receptor desensitization and intracellular calcium determination through simulation

Abstract

One of the crucial processes in preventing cellular damage due to excitotoxicity involves the calcium-mediated desensitization of the N-methyl-D-aspartate (NMDA) receptor. The opening of NMDA channels results in the influx of Na+ and Ca2+ ions and efflux of K+ ions. This condition leads to an increase in intracellular calcium ([Ca2+]i), thereby diminishing the NMDA current and preventing damage induced by constant stimulation of the receptor by glutamate. In this study, a simulator based on a phenomenological mathematical model was developed, employing the Visual Basic 6.0 language for the Windows® environment. Input variables encompass intracellular calcium, peak currents (Ip), and steady-state currents (Iss). Input currents were derived from previously published electrophysiological recordings. The simulator adeptly reproduces the NMDA receptor desensitization phenomenon under varying experimental conditions and accurately calculates internal calcium with a 10% margin of error. It proves valuable in scenarios where simultaneous recordings of NMDA current and [Ca2+]i via fluorescence labeling techniques are impractical. In the realm of education, it enables students to conduct virtual experiments, providing an immersive introduction to the topic.