Ionotropic receptors and ion channels in ischemic neuronal death and dysfunction

• Published in: Acta pharmacologica Sinica Vol. 34; no. 1; pp. 39 - 48
• Main Authors: Weilinger, Nicholas L, Maslieieva, Valentyna, Bialecki, Jennifer, Sridharan, Sarup S, Tang, Peter L, Thompson, Roger J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2013; Nature Publishing Group
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Brain - blood supply; Brain - metabolism; Brain - pathology; Brain Ischemia - etiology; Brain Ischemia - metabolism; Brain Ischemia - pathology; Cell Death; Connexins - metabolism; Humans; Immunology; Internal Medicine; Ion Channels - metabolism; Medical Microbiology; Neurons - metabolism; Neurons - pathology; NMDA受体; Pharmacology/Toxicology; Receptors, Purinergic - metabolism; Review; Stroke - complications; Stroke - metabolism; Stroke - pathology; Vaccine; 功能障碍; 神经元; 离子型; 离子通道; 细胞死亡; 缺血; 谷氨酸受体; P2X7 receptors; anoxic depolarization; ionotropic receptors; pannexin channels; NMDA receptors; stroke; acid-sensing ion channels (ASICs); ion channels; TRP channels
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2012.95

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 ionotro- pic 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 （Panxl） ion chan- nel. We also discuss the important roles of transient receptor potential （TRP） channels and acid-sensing ion channels （ASICs） in res- ponses 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.