Articles: acid-sensing-ion-channels-metabolism.
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Migraine is the most common neurological disorder and one of the most common chronic pain conditions. Despite its prevalence, the pathophysiology leading to migraine is poorly understood and the identification of new therapeutic targets has been slow. Several processes are currently thought to contribute to migraine including altered activity in the hypothalamus, cortical-spreading depression (CSD), and afferent sensory input from the cranial meninges. ⋯ Although few studies have directly examined a role of ASICs in migraine, studies directly examining a connection have generated promising results including efficacy of ASIC blockers in both preclinical migraine models and in human migraine patients. The purpose of this review is to discuss the pathophysiology thought to contribute to migraine and findings that implicate decreased pH and/or ASICs in these events, as well as propose issues to be resolved in future studies of ASICs and migraine. This article is part of the Special Issue entitled 'Acid-Sensing Ion Channels in the Nervous System'.
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The acid-sensing ion channel (ASIC) has emerged as a novel type of ion channel that is activated by extracellular protons as well as nonproton ligands. Advances in ASIC research have resolved its multifaceted structural and functional properties, including its widespread distribution, polymodal activation, and activity-dependent regulation of its expression. ⋯ Here we review the contribution of ASICs at the peripheral and central levels to the development of acute pain, inflammatory pain, neuropathic pain, and anxiety-related disorders, as well as their potential underlying mechanisms. Accumulating evidence suggests that ASICs represent a novel class of promising targets for developing effective therapies for pain and anxiety.
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Progress in neurobiology · Apr 2014
ReviewProton-sensitive cation channels and ion exchangers in ischemic brain injury: new therapeutic targets for stroke?
Ischemic brain injury results from complicated cellular mechanisms. The present therapy for acute ischemic stroke is limited to thrombolysis with the recombinant tissue plasminogen activator (rtPA) and mechanical recanalization. Therefore, a better understanding of ischemic brain injury is needed for the development of more effective therapies. ⋯ In this review, we summarize recent pre-clinical experimental research findings on how these channels/exchangers are regulated in both in vitro and in vivo models of cerebral ischemia. The blockade or transgenic knockdown of these proteins was shown to be neuroprotective in these ischemia models. Taken together, these non-NMDA receptor-dependent mechanisms may serve as novel therapeutic targets for stroke intervention.