Calcium homeostasis pathways in cortical neurons

Calcium homeostasis in cortical neurons refers to the complex set of mechanisms that maintain intracellular calcium concentrations ([Ca2+]i) within a narrow physiological range, typically around 100 nM at rest [3]. This regulation is achieved through a balance of calcium influx via plasma membrane channels like voltage-gated calcium channels (VGCCs) and N-methyl-D-aspartate (NMDA) receptors, efflux via pumps and exchangers such as the plasma membrane Ca2+ ATPase (PMCA) and sodium-calcium exchanger (NCX), and sequestration into or release from intracellular stores like the endoplasmic reticulum (via SERCA, RyR, and IP3R) and mitochondria [5, 7]. In cortical neurons, calcium serves as a critical second messenger for synaptic plasticity, gene expression, and neurotransmitter release [3, 8]. Dysregulation of these pathways, often termed calcium dyshomeostasis, is a hallmark of neurodegenerative diseases such as Alzheimer's and Parkinson's, where chronic elevation of cytosolic calcium leads to excitotoxicity, mitochondrial dysfunction, and eventual neuronal death [1, 9]. Therapeutic strategies targeting these pathways aim to restore calcium balance using various modulators, including NMDAR antagonists and calcium channel blockers [2, 9].

Other names

Neuronal calcium signalingIntracellular calcium regulationCalcium dyshomeostasisNeuronal calcium homeostasis

Modulation of calcium influx (e.g., via N-methyl-D-aspartate receptor or voltage-gated calcium channel blockade), efflux (e.g., via plasma membrane Ca2+ ATPase activation), or internal sequestration (e.g., via ryanodine receptor antagonism) to restore physiological calcium levels and prevent excitotoxicity [1, 9].