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Acid-Sensing Ion Channels and Synaptic Plasticity: A Revisit
Published in Tian-Le Xu, Long-Jun Wu, Nonclassical Ion Channels in the Nervous System, 2021
Ming-Gang Liu, Michael X. Zhu, Tian-Le Xu
As introduced above, ASICs encompass a family of ion channels with several isoforms, among which ASIC1a, ASIC2a, ASIC2b and ASIC4 are all highly expressed in the central nervous system1,36. However, a large number of previous research on ASICs and synaptic plasticity have concentrated on the function of ASIC1a, with other isoforms being much less studied. Although ASIC2a has been shown to promote surface trafficking of ASIC1a53, the exact roles of ASIC2a in different forms of synaptic plasticity are still not clear. Thus, future studies may be designed to evaluate the functions of homomeric or heteromeric ASIC2 isoforms in synaptic transmission and plasticity in various brain regions under a variety of physiological or pathological conditions.
Retinal pH and Acid Regulation During Metabolic Acidosis
Published in Current Eye Research, 2018
Alyssa Dreffs, Desmond Henderson, Andrey V. Dmitriev, David A. Antonetti, Robert A. Linsenmeier
Similarly, the ASICs may have a variety of functions. ASICs are nonclassical, H+-gated cation channels.40 Several isoforms (ASIC1a and ASIC1b, ASIC2a and ASIC2b, ASIC3 and ASIC4) are found in inner and outer retinal neurons as well as Müller cells.41,42 Their roles are not completely understood, but they appear to play a role in cell survival and other functions. Deletion of ASIC2a24 or ASIC323 increases the amplitude of the ERG, but knockout of either one leads to subsequent retinal degeneration. On the other hand, the presence of ASIC1 leads to degeneration under some conditions, as noted below, and its upregulation in acidosis may be detrimental, in contrast to the upregulation of CA, AEP-3, and NHE-1, which are more likely protective. Acidosis opens ASIC1, allowing Ca+2 entry into cultured mouse hippocampal cells, an effect that is significantly reduced in ASIC1 knockouts.43 Ca+2 entry is not associated with other ASICs.43 Blocking ASIC1a with a specific antagonist prevents ganglion cell damage caused by hypoxia25 or by chloroquine.44 Similarly, ganglion cell death due to optic nerve ligation was prevented by amiloride,45 another blocker of ASICs, but amiloride blocks NHE-1 as well, so this was a less specific test. However, increased ASIC1 appears from the existing evidence to be detrimental, so the increase in ASIC1 message in this study may suggest a damaging effect of acidosis. Many questions remain about ASICs and their functions, and whether longer-term acidosis would cause the protein levels to increase.
Neuroprotective effects of inhibitors of Acid-Sensing ion channels (ASICs) in optic nerve crush model in rodents
Published in Current Eye Research, 2018
Dorota L. Stankowska, Brett H. Mueller, Hidehiro Oku, Tsunehiko Ikeda, Adnan Dibas
Blockade of ASIC1a channels with amiloride or psalmotoxin-1 reduced primary RGC death induced by hypoxia.30 Although ASIC-2 is expressed in RGCs, its role in RGCs is yet to be characterized.31 ASIC2 was minimally expressed in isolated rat primary RGCs (Dibas et al., unpublished observations). Although ASIC3 is detected in RGCs, it did not significantly contribute to ASIC currents recorded in cultured RGCs32 and therefore was not studied in the current manuscript. Similarly, ASIC4 function in tissues is not known as these channels do not respond to changes in pH.
Neuroprotective Effects of Psalmotoxin-1, an Acid-Sensing Ion Channel (ASIC) Inhibitor, in Ischemia Reperfusion in Mouse Eyes
Published in Current Eye Research, 2018
Adnan Dibas, Cameron Millar, Abraham Al-Farra, Thomas Yorio
Blockade of ASIC1a channels with amiloride or psalmotoxin 1 reduced hypoxia-induced RGC death in vitro.27 However, the role of ASIC-2 in RGC function is yet to be characterized, although it is expressed in RGCs.28 While ASIC3 has been detected in RGCs, it does not significantly contribute to ASIC currents recorded in cultured RGCs.29 Similarly, ASIC4 function in tissues is not known as these channels do not respond to changes in pH. Therefore, ASICs 1 and 2 represent novel therapeutic targets for several clinically important disorders, including glaucoma.