Neuronal calcium homeostasis and dysregulation

Antioxid Redox Signal. 2011 Apr 1;14(7):1261-73. doi: 10.1089/ars.2010.3386. Epub 2010 Nov 30.


The calcium ion (Ca(2+)) is the main second messenger that helps to transmit depolarization status and synaptic activity to the biochemical machinery of a neuron. These features make Ca(2+) regulation a critical process in neurons, which have developed extensive and intricate Ca(2+) signaling pathways. High intensity Ca(2+) signaling necessitates high ATP consumption to restore basal (low) intracellular Ca(2+) levels after Ca(2+) influx through plasma membrane receptor and voltage-dependent ion channels. Ca(2+) influx may also lead to increased generation of mitochondrial reactive oxygen species (ROS). Impaired abilities of neurons to maintain cellular energy levels and to suppress ROS may impact Ca(2+) signaling during aging and in neurodegenerative disease processes. This review focuses on mitochondrial and endoplasmic reticulum Ca(2+) homeostasis and how they relate to synaptic Ca(2+) signaling processes, neuronal energy metabolism, and ROS generation. Also, the contribution of altered Ca(2+) signaling to neurodegeneration during aging will be considered. Advances in understanding the molecular regulation of Ca(2+) homeostasis and how it is perturbed in neurological disorders may lead to therapeutic strategies that modulate neuronal Ca(2+) signaling to enhance function and counteract disease processes.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Aging / metabolism*
  • Amyloid Precursor Protein Secretases / metabolism
  • Animals
  • Calcium / metabolism*
  • Calcium Signaling
  • Endoplasmic Reticulum / metabolism
  • Energy Metabolism
  • Homeostasis
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Mitochondria / metabolism
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Mitochondrial Permeability Transition Pore
  • Neurodegenerative Diseases / metabolism
  • Neurons / metabolism*
  • Reactive Oxygen Species / metabolism
  • Stress, Physiological


  • Inositol 1,4,5-Trisphosphate Receptors
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Reactive Oxygen Species
  • Amyloid Precursor Protein Secretases
  • Calcium