Ionotropic receptors and ion channels in ischemic neuronal death and dysfunction

Abstract

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.

Serum Pro-Oxidant-Antioxidant Balance, Advanced Oxidized Protein Products (AOPP) and Protein Carbonyl in Patients With Stroke

“…In this situation which is defined as hypoxia, the brain cells loss their normal functionalities and metabolism (37)(38)(39). The presence of abundant polyunsaturated fatty acids (40) and lower levels of antioxidant enzymes such as catalase and glutathione peroxidase in brain cells, makes them vulnerable and sensitive to free radicals.…”

Regulation of the Pannexin-1 Promoter in the Rat Epididymis1

“…In the epididymis, PANX1 is located in principal cells, basal cells, and halo cells, while PANX3 is localized at the apical plasma membrane of principal cells [17]. Numerous studies have shown that PANX1 is implicated in the secretion of ATP and works in conjunction with purinergic receptors to regulate ATP secretion and intercellular communication through the propagation of ATP signaling [19,35,[44][45][46]. Hence, the regulation of the Panx1 gene provides an insight into its role and function in epididymal physiology.…”

Functional implications of axon initial segment cytoskeletal disruption in stroke

“…There are also other channels and exchangers that are considered to be activated during ischemia and are permeable to Ca 2+ such as L-type Ca 2+ channels, acid-sensing ion channels (ASICs),Na + /Ca 2+ exchangers (NCX) and P2X7 channels [99] sensitive to extracellular ATP concentrations (reviewed in Ref [100] ). P2X7 channels are considered to be activated in neuronal injury due to high extracellular concentrations of ATP and its metabolites under ischemic conditions [99] , but the activation is not sufficient to cause neuronal death alone [101] .…”