Acid Sensing Ion Channel 1a (ASIC1a) Mediates Activity-induced Pain by Modulation of Heteromeric ASIC Channel Kinetics

Gregory, Nicholas S.; Gautam, Mamta; Benson, Christopher J.; Sluka, Kathleen A.

doi:10.1016/j.neuroscience.2018.06.033

Cited by 22 publications

(20 citation statements)

References 39 publications

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“…Our finding that ASIC1a contributes to the mechanoreflex in HF‐rEF is consistent with a growing body of literature suggesting that ASIC1a stimulation may modulate the function of mechanically activated channels on the sensory endings of thin fibre muscle afferents under various physiological conditions (Chen & Wong, 2013; Gregory et al., 2018; Page et al., 2004; Ruan et al., 2021). For example, ASIC1a blockade with PcTx‐1 has been shown to prevent the development of mechanical hyperalgesia following activity‐induced pain in the mouse (Gregory et al., 2018). Additionally, ASIC1 knockout mice are resistant to the typical development of mechanical hyperalgesia following injection of the inflammation‐inducing carrageenan solution into the gastrocnemius muscle (Walder et al., 2010).…”

Section: Discussionsupporting

confidence: 90%

Novel mechanosensory role for acid sensing ion channel subtype 1a in evoking the exercise pressor reflex in rats with heart failure

Butenas

Rollins

Parr

et al. 2022

The Journal of Physiology

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Section: Discussionsupporting

confidence: 90%

Novel mechanosensory role for acid sensing ion channel subtype 1a in evoking the exercise pressor reflex in rats with heart failure

Butenas

Rollins

Parr

et al. 2022

The Journal of Physiology

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“…Of these, six have clear proton sensitivity (Price et al 1996;Waldmann et al 1996Waldmann et al , 1997aLingueglia et al 1997;Chen et al 1998;Grunder et al 2000;Wiemuth et al 2014). ASICs are trimers (although see van Bemmelen et al 2015), with both homo and heterotrimers as feasible arrangements (Benson et al 2002;Bartoiet al 2014;Gregory et al 2018). The ASIC1a subunit has been most thoroughly studied using functional and biophysical methods, since it was the first ASIC clone reported to have proton sensitivity, and is the most widely expressed subunit and the only one for which structural data is available.…”

Section: The Basics Of Asicsmentioning

confidence: 99%

Coupling structure with function in acid‐sensing ion channels: challenges in pursuit of proton sensors

Rook

Musgaard

MacLean

2020

The Journal of Physiology

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Acid-sensing ion channels (ASICs) are a class of trimeric cation-selective ion channels activated by changes in pH within the physiological range. They are widely expressed in the central and peripheral nervous systems where they participate in a range of physiological and pathophysiological situations such as learning and memory, pain sensation, fear and anxiety, substance abuse and cell death. ASICs are localized to cell bodies and dendrites, including the postsynaptic density, and within the last 5 years several examples of proton-evoked ASIC excitatory postsynaptic currents have emerged. Thus, ASICs have become bona fide neurotransmitter-gated ion channels, activated by the smallest neurotransmitter possible: protons. Here we review how protons are thought to drive the conformational changes associated with ASIC activation and desensitization. In particular, we weigh the evidence for and against the so-called 'acidic pocket' being a vital proton sensor and discuss the emerging role of the β11-12 linker as a desensitization switch or 'molecular clutch'. We also examine how proton-induced conformational changes pose unique challenges to classical molecular dynamics simulations, as well as some possible solutions. Matthew Rook received his Bachelor of Science degree in pharmacology and toxicology from the University at Buffalo. He is currently a PhD candidate in the laboratory of Dr David MacLean at the University of Rochester Medical Centre within the Department of Pharmacology and Physiology. His primary research project is to define the conformational changes required for acid-sensing ion channel activation and desensitization using fast-perfusion electrophysiology and genetic code expansion.

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“…But, ASIC1a, sensitive to pH level and Ca 2+ -H + related channel, which is involved in the pathogenesis of central nervous system diseases [19], did not show obvious enhancement or weakening in the IPPH group as OTR. In study of musculoskeletal ASIC1a was considered a key and may be a pharmacological target for treatment of musculoskeletal pain when in acid environment [20].This research results could remind us that acidosis state in myometrium previously expected might be not existing under IPPH or even MODS, DIC state. It might be related to the passive expansion of myometrium in third tremster and the local slightly acidic environment.…”

Section: Discussionmentioning

confidence: 52%

Lost OTR Expression and HIF-1α Self-protection in Myometrium of Intractable Postpartum Hemorrhage

Chen

Wang

et al. 2021

Preprint

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Objective: In intractable postpartum hemorrhage(IPPH), uterotonic lost efficacy in myometrum contraction formation. While the key target in uterotonic, OTR(oxytocin receptor) and internal environment in myometrum might have some changes when IPPH. Methods: Three groups of myometrial tissue at different contraction states were collected:(1) term not at labour (TNL) group(10 cases); (2) term at labour (TAL) group(10 cases);(3) intractable postpartum hemorrhage(IPPH) group(10 cases).Expressions of OTR and internal environment markers(ASIC1a ,HIF1α, GlUT, FATP and apoptosis ) were compared in 3 groups by Immunoreactivity Scores method. Results: The expression of OTR in myometrium in IPPH group was 100% negative ,compared to 30%,20% in TNL and TAL group(p < 0.05).70% positive HIF-1α expression in TNL group increased to 80% in TAL group,but decreased to 20% in IPPH group(P<0.05). While the positive expressions of ASIC1a, FATP and GLUT in three groups all had no significant difference.But the apoptosis related markers Bax,caspase-3 and caspase-9 positive expressions in IPPH were significantly all decreased(10%,10%,0%) compared to TNL and TAL group,compared to a high positive expression of Bcl-2 in 3 groups.Conclusion: OTR expression and HIF-1α self-protection might be lost in myometrium of IPPH, which could lead to uterotonic lost efficacy and conservative treatment failure.

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Acid Sensing Ion Channel 1a (ASIC1a) Mediates Activity-induced Pain by Modulation of Heteromeric ASIC Channel Kinetics

Cited by 22 publications

References 39 publications

Novel mechanosensory role for acid sensing ion channel subtype 1a in evoking the exercise pressor reflex in rats with heart failure

Novel mechanosensory role for acid sensing ion channel subtype 1a in evoking the exercise pressor reflex in rats with heart failure

Coupling structure with function in acid‐sensing ion channels: challenges in pursuit of proton sensors

Lost OTR Expression and HIF-1α Self-protection in Myometrium of Intractable Postpartum Hemorrhage

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