Acid Sensing Ion Channels (Asics): Potential Targets for the Discovery of Novel Therapeutics in Disease Management

Abstract

INTRODUCTIONThe acid-sensing ion channels or ASICs form a distinc branch of he degenerin superfamily (ENaC/DEG) of sodium channels. A leas four ASIC genes have been identified in humans so far, numbered 1-4, wi h a number of splice varian s encoding a o al of nine unique pro eins [1][2][3][4][5][6][7][8][9]. The channels formed by he ASIC pro eins are basically pro on-ga ed cation channels, opening rapidly in he presence of ex racellular acid. All ASIC subuni consis s of a large ex racellular domain, 2 ransmembrane helices, and shor cy oplasmic N and C ermini. Functional ASICs are homo or he ero rimers of ASIC1a, ASIC1bASIC2a, ASIC2b, and/ or ASIC3 subuni s [10][11]. ASIC2b is no functional as homomultimer bu form functional he eromeric channels in combination wi h o her subuni s [12]. The activi y of ASIC4 channel has been de ec ed very limi ed ye . I may participa e in regulating he membrane availabili y of o her ASIC subuni s [13]. ASIC1a and ASIC3 are activa ed by an acidi y range (pH 7.0-6.0) observed in several acu e and chronic pain conditions. ASIC3 is particularly sensitive o lactic acidosis and hus is considered o be an impor an componen of acid induced pain [14].Corresponding author: Debendra Nath Roy, Department of Pharmacy, Faculty of Biological Science and Technology, Jessore University of Science and Technology, Jessore-7408, Bangladesh. Email: roydn009@gmail.com I has been noticed ha he activation of ASIC in neurons induce action po entials. The ex en and duration of he ASIC-media ed depolarization depends bo h on ASIC ampli ude activi y and he number of charges he channels ranspor during heir opening [15][16]. Among all o hers, ASIC3 is he mos sensitive o increases in pro on concen ration, wi h half-maximal pH activation is 6.4 [17]. ASIC2 is he leas sensitive, requiring exposure o pH 4.5 for halfmaximal activation. ASICs have been de ec ed hroughou he nervous sys em, specifically in areas of high synaptic densi y, localizing primarily o he soma and processes of neurons [18][19]. Their expression pattern has sugges ed ha hese channels play a role in sensory perception and various neural processes [20][21]. ASICs have widespread dis ribution o many regions in he nervous sys em including dorsal roo ganglia, cor ex, hippocampus, basal ganglia, amygdale, olfac ory bulb, cerebrum and elsewhere [22 -24]. In erestingly, ASICs are increasingly being de eced in nonneuronal settings including cancer cells [25], bone [26], in estinal and bladder epi helium cells and smoo h muscle [27][28][29][30]. Because ASICs are permeable o Na+, heir activation leads o membrane depolarization, hus inducing action po entials in neurons ASICs often have an activation effec on neurons. A s rong ASIC-media ed depolarization, however, can inhibi an already actively signaling neuron. ASIC1a has a small permeabili y for Ca2+ in addition o i s Na+ permeabili y, and some of i s cellular functions, as for example neurodegeneration after ischem- ABSTRACTAcid sensing ion channels (ASIC) are Na+ channels activa ed by ex ernal pro o...

Systemic toxicity of chloroquine and hydroxychloroquine: prevalence, mechanisms, risk factors, prognostic and screening possibilities

“…1). Indeed, 4-AQ inhibits the recognition of nucleic acids by TLRs (Toll-Like Receptor), the MHC (Major Histocompatibility Complex) class II-mediated antigen presentation, inflammation-induced cell proliferation, and antiphospholipid antibodies activity, which are major aspects of the pathophysiology of systemic lupus erythematosus for example [4][5][6][7][8][9][10][11][12][13]. But their action is not limited to the regulation of immunity: 4-AQ acts at the heart of the regulation of other primordial physiological functions, such as lipid and glucose metabolism, hemostasis, vasoactivity, and tumor control.…”