Acidotoxicity in brain ischaemia. (25th October 2006)

• Record Type: Journal Article
• Authors: Simon, R.; Xiong, Z.
• Is Part Of: Biochemical Society transactions. Volume 34:Number 6(2006)
• Page Start: 1356
• Page End: 1361
• Publication Date: 2006-10-25
• Subjects: acid-sensing ion channel (ASIC) -- acidotoxicity -- brain ischaemia -- calcium -- glutamate -- injury; Biochemistry -- Congresses; 572
• DOI: 10.1042/BST0341356
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : Intracellular calcium toxicity remains the central feature in the pathophysiology of ischaemic cell death in brain. Glutamate-gated channels have been thought to be the major sites of ischaemia-induced toxic calcium entry, but the failure of glutamate antagonists in clinical trials has suggested that glutamate-independent mechanisms of calcium entry during ischaemia must exist and may prove central to ischaemic injury. We have shown that ASICs (acid-sensing ion channels) in brain are glutamate-independent vehicles of calcium flux and transport calcium in greater measure in the setting of the two major neurochemical components of ischaemia: acidosis and substrate depletion. Pharmacological blockade of ASICs markedly attenuates stroke injury with a robust therapeutic time window of 5 h following stroke onset. Here, we describe this new mechanism of calcium toxicity in brain ischaemia and offer a potential new therapy for stroke.