Modes of Neuronal Calcium Entry and Homeostasis following Cerebral Ischemia

Abstract

One of the major instigators leading to neuronal cell death and brain damage following cerebral ischemia is calcium dysregulation. The neuron's inability to maintain calcium homeostasis is believed to be a result of increased calcium influx and impaired calcium extrusion across the plasma membrane. The need to better understand the cellular and biochemical mechanisms of calcium dysregulation contributing to neuronal loss following stroke/cerebral ischemia is essential for the development of new treatments in order to reduce ischemic brain injury. The aim of this paper is to provide a concise overview of the various calcium influx pathways in response to ischemia and how neuronal cells attempts to overcome this calcium overload.

Figure 1

Modes of calcium entry and exit into neurons following cerebral ischemia. Modes of calcium entry (top of cell diagram) are VDCCs (voltage-dependent calcium channel), glutamate receptors (NMDA, AMPA, KA, and mGluR), SOCE (store-operated intracellular calcium entry), TRP (transient receptor potential channels), ASIC (acid-sensing ion channels), I_EIC (inward excitotoxic injury current calcium-permeable channels), and NCX (sodium-calcium exchanger operating in entry mode). Calcium can also be sequestered intracellularly (middle of cell diagram) by the mitochondria and ER (endoplasmic reticulum). Modes of calcium exit (bottom of cell diagram) are PCMA (Calcium ATPase pump) and NCX (sodium-calcium exchanger operating in exit mode).