Review

Loss of endoplasmic reticulum Ca2+ homeostasis: contribution to neuronal cell death during cerebral ischemia

Authors: Ankur Bodalia, Hongbin Li, Michael F Jackson
DOI: 10.1038/aps.2012.139

Abstract

Ankur BODALIA1, Hongbin LI2, Michael F JACKSON1, 2, *

1Department of Physiology and Pharmacology, Western University, London, ON, Canada N6A 5K8; 2Robarts Research Institute, Molecular Brain Research Group, Western University, London, ON, Canada N6A 5K8

Loss of energy supply to neurons during stroke induces a rapid loss of membrane potential that is called the anoxic depolarization. Anoxic depolarizations result in tremendous physiological stress on the neurons because of the dysregulation of ionic fluxes and the loss of ATP to drive ion pumps that maintain electrochemical gradients. In this review, we present an overview of some of the ionotropic receptors and ion channels that are thought to contribute to the anoxic depolarization of neurons and subsequently, to cell death. The ionotropic receptors for glutamate and ATP that function as ligand-gated cation channels are critical in the death and dysfunction of neurons. Interestingly, two of these receptors (P2X7 and NMDAR) have been shown to couple to the pannexin-1 (Panx1) ion channel. We also discuss the important roles of transient receptor potential (TRP) channels and acid-sensing ion channels (ASICs) in responses to ischemia. The central challenge that emerges from our current understanding of the anoxic depolarization is the need to elucidate the mechanistic and temporal interrelations of these ion channels to fully appreciate their impact on neurons during stroke.

Keywords: stroke; anoxic depolarization; ionotropic receptors; NMDA receptors; P2X7 receptors; ion channels; pannexin channels; TRP channels; acid-sensing ion channels (ASICs)

Funding from the Canadian Institutes of Health Research, Alberta Innovates — Health Solutions (AIHS), Heart and Stroke Foundation of Canada, and the Canadian Stroke Network, supports research in the Thompson lab. RJT holds a Scholar award from AIHS and a New Investigator Award from the Heart and Stroke Foundation of Canada. NLW holds an AIHS studentship. SSS was the recipient of a Canadian Stroke Network Summer Studentship.
* To whom correspondence should be addressed.
E-mail rj.thompson@ucalgary.ca
Received 2012-04-06 Accepted 2012-06-08
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