Molecular dynamics and functional studies define a hot spot of crystal contacts essential for PcTx1 inhibition of acid-sensing ion channel 1a

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Molecular dynamics and functional studies define a hot spot of crystal contacts essential for PcTx1 inhibition of acid-sensing ion channel 1a.

BACKGROUND AND PURPOSE The spider-venom peptide PcTx1 is the most potent and selective inhibitor of acid-sensing ion channel (ASIC) 1a. It has centrally acting analgesic activity and is neuroprotective in rodent models of ischaemic stroke. Understanding the molecular details of the PcTx1 : ASIC1a interaction should facilitate development of therapeutically useful ASIC1a modulators. Previously, ...

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Objective(s): Activation of acid-sensing ion channel 1a (ASIC1a) is responsible for tissue injury caused by acidosis in nervous systems. But its physiological and pathological roles in nucleus pulposus cells (NPCs) are unclear. The aim of this study is to investigate whether ASIC1a regulates the survival of NPCs in the acidic environment of degenerated discs. Materials and Methods: NPCs were i...

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Although acid-sensitive ion channels (ASICs) play an important role in brain functions, the exact mechanism of their physiological activation remain unclear. A possible answer to the intriguing question is that some presently unknown endogenous ligand(s) positively modulate ASICs and enhance their responses to physiologically significant level. In the present work we found that histamine select...

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Acid-sensing ion channels (ASICs) are neuronal Na(+) channels that are members of the epithelial Na(+) channel/degenerin family and are transiently activated by extracellular acidification. ASICs in the central nervous system have a modulatory role in synaptic transmission and are involved in cell injury induced by acidosis. We have recently demonstrated that ASIC function is regulated by serin...

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Acid-sensing ion channel 1b (ASIC1b) is expressed in peripheral sensory neurons and has been implicated in nociception. Understanding the modulation of ASIC1b will provide important insight into how ASIC1b contributes to pain sensation. In our previous study, we showed that zinc, an important modulator of pain sensation, reduces rat ASIC1b current. However, rat ASIC1b shows several important di...

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ژورنال

عنوان ژورنال: British Journal of Pharmacology

سال: 2015

ISSN: 0007-1188

DOI: 10.1111/bph.13267