Acid-sensing ion channels in mouse olfactory bulb M/T neurons

Li, Ming Hua; Liu, Selina Qiuying; Inoue, Kōichi; Lan, Jinquan; Simon, Roger P.; Xiong, Zhi Gang

doi:10.1085/jgp.201310990

Cited by 12 publications

(14 citation statements)

References 60 publications

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“…Fifth, the EC50 of pH activation of anterior pituitary cell currents (pH 6.1) is in the range of that for homomeric ASIC1a (EC 50 = pH 5.8) and ASIC1a/2a (EC 50 = pH 5.5) and ASIC1a/2b (EC 50 = pH 6.2) heteromultimers [28] . Currents generated by ASIC heteromultimers would be consistent with previous studies indicating that heteromultimers of subunits account for most neuronal H + -gated current in DRG neurons [46] , [54] , hippocampal neurons [31] , [35] , [55] , cerebellar purkinje neurons [29] , suprachiasmatic nucleus neurons [33] , PC12 cells [26] , cortical neurons [24] , olfactory bulb mitral/tufted neurons [27] and dorsal horn neurons [30] .…”

Section: Discussionsupporting

confidence: 91%

“…Previous studies indicate that Zn 2+ potentiates homomeric and heteromultimeric channels that contain ASIC2a (ASIC2a, ASIC1a/2a, and ASIC2a/3) in the micromolar range [27] , [39] , but inhibit homomeric ASIC1a channels in the nanomolar range and ASIC3 channels in the micromolar range [40] , [41] . Thus, to gain further insight into pituitary ASIC channel properties, we tested the effects of Zn 2+ on freshly isolated anterior pituitary cells.…”

Section: Resultsmentioning

confidence: 98%

“…Amiloride, a non-specific ASIC blocker, inhibits ASIC currents in many cell types [1] , [24] , [26] , [27] , [29] – [33] . We found that amiloride also inhibited ASIC currents in anterior pituitary cells ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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Expression and Activity of Acid-Sensing Ion Channels in the Mouse Anterior Pituitary

Reznikov

Welsh

2014

PLoS ONE

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Acid sensing ion channels (ASICs) are proton-gated cation channels that are expressed in the nervous system and play an important role in fear learning and memory. The function of ASICs in the pituitary, an endocrine gland that contributes to emotions, is unknown. We sought to investigate which ASIC subunits were present in the pituitary and found mRNA expression for all ASIC isoforms, including ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3 and ASIC4. We also observed acid-evoked ASIC-like currents in isolated anterior pituitary cells that were absent in mice lacking ASIC1a. The biophysical properties and the responses to PcTx1, amiloride, Ca2+ and Zn2+ suggested that ASIC currents were mediated predominantly by heteromultimeric channels that contained ASIC1a and ASIC2a or ASIC2b. ASIC currents were also sensitive to FMRFamide (Phe-Met-Arg-Phe amide), suggesting that FMRFamide-like compounds might endogenously regulate pituitary ASICs. To determine whether ASICs might regulate pituitary cell function, we applied low pH and found that it increased the intracellular Ca2+ concentration. These data suggest that ASIC channels are present and functionally active in anterior pituitary cells and may therefore influence their function.

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Section: Discussionsupporting

confidence: 91%

Section: Resultsmentioning

confidence: 98%

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Expression and Activity of Acid-Sensing Ion Channels in the Mouse Anterior Pituitary

Reznikov

Welsh

2014

PLoS ONE

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“…These numbers correlate well with our prediction, which shows that, in striatum, ASIC1a homomers, 2-1a:1-2a, and 1-1a:2-2a heteromers, constitute to 60.5 %, 33 %, and 6 % of functional ASICs, respectively. In addition, acid-activated currents in neurons from other brain regions, including hippocampus, cortex and olfactory bulb exhibit a mixed contribution from ASIC1a homomers and 1a/2a heteromers [ 18 , 21 , 23 ]. Again, these results fit with our prediction (Table 1 ).…”

Section: Discussionmentioning

confidence: 99%

ASIC subunit ratio and differential surface trafficking in the brain

Jiang

et al. 2016

Mol Brain

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BackgroundAcid-sensing ion channels (ASICs) are key mediators of acidosis-induced responses in neurons. However, little is known about the relative abundance of different ASIC subunits in the brain. Such data are fundamental for interpreting the relative contribution of ASIC1a homomers and 1a/2 heteromers to acid signaling, and essential for designing therapeutic interventions to target these channels. We used a simple biochemical approach and semi-quantitatively determined the molar ratio of ASIC1a and 2 subunits in mouse brain. Further, we investigated differential surface trafficking of ASIC1a, ASIC2a, and ASIC2b.Results and conclusionsASIC1a subunits outnumber the sum of ASIC2a and ASIC2b. There is a region-specific variation in ASIC2a and 2b expression, with cerebellum and striatum expressing predominantly 2b and 2a, respectively. Further, we performed surface biotinylation and found that surface ASIC1a and ASIC2a ratio correlates with their total expression. In contrast, ASIC2b exhibits little surface presence in the brain. This result is consistent with increased co-localization of ASIC2b with an ER marker in 3T3 cells. Our data are the first semi-quantitative determination of relative subunit ratio of various ASICs in the brain. The differential surface trafficking of ASICs suggests that the main functional ASICs in the brain are ASIC1a homomers and 1a/2a heteromers. This finding provides important insights into the relative contribution of various ASIC complexes to acid signaling in neurons.

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“…35 Acute isolation of cerebellar granule neurons and cortical neurons was performed similar to what was described previously. 35,36 Briefly, adult mice (10-12 weeks) were anesthetized with isoflurane followed by cervical dislocation and decapitation. The brain tissues were dissected, sliced at 1-mm thickness, and incubated in oxygenated extracellular solution containing 3.5 mg/ml papain for 30 or 60 min for cortical or cerebellar granule neurons, respectively.…”

Section: Focal Ischemiamentioning

confidence: 99%

Region specific contribution of ASIC2 to acidosis-and ischemia-induced neuronal injury

Jiang

Leng

et al. 2016

J Cereb Blood Flow Metab

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Acidosis in the brain plays a critical role in neuronal injury in neurological diseases, including brain ischemia. One key mediator of acidosis-induced neuronal injury is the acid-sensing ion channels (ASICs). Current literature has focused on ASIC1a when studying acid signaling. The importance of ASIC2, which is also widely expressed in the brain, has not been appreciated. We found here a region-specific effect of ASIC2 on acid-mediated responses. Deleting ASIC2 reduced acid-activated current in cortical and striatal neurons, but had no significant effect in cerebellar granule neurons. In addition, we demonstrated that ASIC2 was important for ASIC1a expression, and that ASIC2a but not 2b facilitated ASIC1a surface trafficking in the brain. Further, we showed that ASIC2 deletion attenuated acidosis/ischemia-induced neuronal injury in organotypic hippocampal slices but had no effect in organotypic cerebellar slices. Consistent with an injurious role of ASIC2, we showed that ASIC2 deletion significantly protected the mouse brain from ischemic damage in vivo. These data suggest a critical region-specific contribution of ASIC2 to neuronal injury and reveal an important functional difference between ASIC2a and 2b in the brain.

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Acid-sensing ion channels in mouse olfactory bulb M/T neurons

Abstract: Functional acid-sensing ion channels are present in olfactory bulb neurons and may contribute to normal olfaction.

Cited by 12 publications

References 60 publications

Expression and Activity of Acid-Sensing Ion Channels in the Mouse Anterior Pituitary

Expression and Activity of Acid-Sensing Ion Channels in the Mouse Anterior Pituitary

ASIC subunit ratio and differential surface trafficking in the brain

Region specific contribution of ASIC2 to acidosis-and ischemia-induced neuronal injury

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