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Wijerathne, Tharaka Darshana,Kim, Ji Hyun,Kim, Min Ji,Kim, Chul Young,Chae, Mee Ree,Lee, Sung Won,Lee, Kyu Pil The Korean Society of Pharmacology 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.5
Sperm function and male fertility are closely related to pH dependent $K^+$ current (KSper) in human sperm, which is most likely composed of Slo3 and its auxiliary subunit leucine-rich repeat-containing protein 52 (LRRC52). Onion peel extract (OPE) and its major active ingredient quercetin are widely used as fertility enhancers; however, the effect of OPE and quercetin on Slo3 has not been elucidated. The purpose of this study is to investigate the effect of quercetin on human Slo3 channels. Human Slo3 and LRRC52 were co-transfected into HEK293 cells and pharmacological properties were studied with the whole cell patch clamp technique. We successfully expressed and measured pH sensitive and calcium insensitive Slo3 currents in HEK293 cells. We found that OPE and its key ingredient quercetin inhibit Slo3 currents. Inhibition by quercetin is dose dependent and this degree of inhibition decreases with elevating internal alkalization and internal free calcium concentrations. Functional moieties in the quercetin polyphenolic ring govern the degree of inhibition of Slo3 by quercetin, and the composition of such functional moieties are sensitive to the pH of the medium. These results suggest that quercetin inhibits Slo3 in a pH and calcium dependent manner. Therefore, we surmise that quercetin induced depolarization in spermatozoa may enhance the voltage gated proton channel (Hv1), and activate non-selective cation channels of sperm (CatSper) dependent calcium influx to trigger sperm capacitation and acrosome reaction.
Wijerathne, Tharaka Darshana,Kim, Jihyun,Yang, Dongki,Lee, Kyu Pil The Korean Society of Pharmacology 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.2
Plasma membrane hyperpolarization associated with activation of $Ca^{2+}$-activated $K^+$ channels plays an important role in sperm capacitation during fertilization. Although Slo3 (slowpoke homologue 3), together with the auxiliary ${\gamma}^2$-subunit, LRRC52 (leucine-rich-repeat-containing 52), is known to mediate the pH-sensitive, sperm-specific $K^+$ current KSper in mice, the molecular identity of this channel in human sperm remains controversial. In this study, we tested the classical $BK_{Ca}$ activators, NS1619 and LDD175, on human Slo3, heterologously expressed in HEK293 cells together with its functional interacting ${\gamma}^2$ subunit, hLRRC52. As previously reported, Slo3 $K^+$ current was unaffected by iberiotoxin or 4-aminopyridine, but was inhibited by ~50% by 20 mM TEA. Extracellular alkalinization potentiated hSlo3 $K^+$ current, and internal alkalinization and $Ca^{2+}$ elevation induced a leftward shift its activation voltage. NS1619, which acts intracellularly to modulate hSlo1 gating, attenuated hSlo3 $K^+$ currents, whereas LDD175 increased this current and induced membrane potential hyperpolarization. LDD175-induced potentiation was not associated with a change in the half-activation voltage at different intracellular pHs (pH 7.3 and pH 8.0) in the absence of intracellular $Ca^{2+}$. In contrast, elevation of intracellular $Ca^{2+}$ dramatically enhanced the LDD175-induced leftward shift in the half-activation potential of hSlo3. Therefore, the mechanism of action does not involve pH-dependent modulation of hSlo3 gating; instead, LDD175 may modulate $Ca^{2+}$-dependent activation of hSlo3. Thus, LDD175 potentially activates native KSper and may induce membrane hyperpolarization-associated hyperactivation in human sperm.
Tharaka Darshana Wijerathne,김지현,양동기,이규필 대한약리학회 2017 The Korean Journal of Physiology & Pharmacology Vol.21 No.2
Plasma membrane hyperpolarization associated with activation of Ca2+-activated K+ channels plays an important role in sperm capacitation during fertilization. Although Slo3 (slowpoke homologue 3), together with the auxiliary g2- subunit, LRRC52 (leucine-rich-repeat–containing 52), is known to mediate the pHsensitive, sperm-specific K+ current KSper in mice, the molecular identity of this channel in human sperm remains controversial. In this study, we tested the classical BKCa activators, NS1619 and LDD175, on human Slo3, heterologously expressed in HEK293 cells together with its functional interacting g2 subunit, hLRRC52. As previously reported, Slo3 K+ current was unaffected by iberiotoxin or 4-aminopyridine, but was inhibited by ~50% by 20 mM TEA. Extracellular alkalinization potentiated hSlo3 K+ current, and internal alkalinization and Ca2+ elevation induced a leftward shift its activation voltage. NS1619, which acts intracellularly to modulate hSlo1 gating, attenuated hSlo3 K+ currents, whereas LDD175 increased this current and induced membrane potential hyperpolarization. LDD175-induced potentiation was not associated with a change in the half-activation voltage at different intracellular pHs (pH 7.3 and pH 8.0) in the absence of intracellular Ca2+. In contrast, elevation of intracellular Ca2+ dramatically enhanced the LDD175-induced leftward shift in the half-activation potential of hSlo3. Therefore, the mechanism of action does not involve pH-dependent modulation of hSlo3 gating; instead, LDD175 may modulate Ca2+-dependent activation of hSlo3. Thus, LDD175 potentially activates native KSper and may induce membrane hyperpolarization-associated hyperactivation in human sperm.
Tharaka Darshana Wijerathne,Ji Hyun Kim,Min Ji Kim,Chul Young Kim,Mee Ree Chae,Sung Won Lee,Kyu Pil Lee 대한약리학회 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.5
Sperm function and male fertility are closely related to pH dependent K+ current (KSper) in human sperm, which is most likely composed of Slo3 and its auxiliary subunit leucine-rich repeat-containing protein 52 (LRRC52). Onion peel extract (OPE) and its major active ingredient quercetin are widely used as fertility enhancers; however, the effect of OPE and quercetin on Slo3 has not been elucidated. The purpose of this study is to investigate the effect of quercetin on human Slo3 channels. Human Slo3 and LRRC52 were co-transfected into HEK293 cells and pharmacological properties were studied with the whole cell patch clamp technique. We successfully expressed and measured pH sensitive and calcium insensitive Slo3 currents in HEK293 cells. We found that OPE and its key ingredient quercetin inhibit Slo3 currents. Inhibition by quercetin is dose dependent and this degree of inhibition decreases with elevating internal alkalization and internal free calcium concentrations. Functional moieties in the quercetin polyphenolic ring govern the degree of inhibition of Slo3 by quercetin, and the composition of such functional moieties are sensitive to the pH of the medium. These results suggest that quercetin inhibits Slo3 in a pH and calcium dependent manner. Therefore, we surmise that quercetin induced depolarization in spermatozoa may enhance the voltage gated proton channel (Hv1), and activate non-selective cation channels of sperm (CatSper) dependent calcium influx to trigger sperm capacitation and acrosome reaction.
Pyrrole Coating with In Situ Polymerization for Piezoresistive Sensor Development - A Review
Dilini Srinika Wijerathne Gunasekara,Xin Niu,Waqar Lqbal,Yin He,Hao Liu 한국고분자학회 2022 Macromolecular Research Vol.30 No.3
Polypyrrole (PPy) is a highly practicing conductive polymer with the potentiality to modify conductivity, sensitivity, and applicability to blend or coated over different materials to offer a wide range of properties, especially for piezoresistive sensors that are highly in demand in smart electronics. The in-situ polymerization is a promising method to prepare PPy coating and composites for cost-effective reliable sensors fabrication that is highly ambitious, for healthcare and rehabilitation purposes with numerous possibilities for modifications. PPy preparation with in-situ polymerization method is still in a great challenge to get desired outcomes so many types of research come out, however not enough records in analysis basis. This research is focused on analyzing different possibilities of PPy with an in-situ polymerization process to get different outcomes related to the change conductivity and sensitivity of PPy coated sensors. As the outcome, this review gives some inspirational ideas to develop high-performance PPy coatings enhancing its conductivity and sensitivity for piezoresistive sensor fabrications.
Kim, Kyu Min,Wijerathne, Tharaka,Hur, Jin-Hoe,Kang, Uk Jung,Kim, Ihn Hyeong,Kweon, Yeong Cheon,Lee, Ah Reum,Jeong, Su Ji,Lee, Sang Kwon,Lee, Yoon Young,Sim, Bo-Woong,Lee, Jong-Hee,Baig, Chunggi,Kim, S National Academy of Sciences 2018 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.115 No.20
<P>Store-operated calcium entry (SOCE), an important mechanism of Ca2+ signaling in a wide range of cell types, is mediated by stromal interaction molecule (STIM), which senses the depletion of endoplasmic reticulum Ca2+ stores and binds and activates Orai channels in the plasma membrane. This inside-out mechanism of Ca2+ signaling raises an interesting question about the evolution of SOCE: How did these two proteins existing in different cellular compartments evolve to interact with each other? We investigated the gating mechanism of Caenorhabditis elegans Orai channels. Our analysis revealed a mechanism of Orai gating by STIM binding to the intracellular 2-3 loop of Orai in C. elegans that is radically different from Orai gating by STIM binding to the N and C termini of Orai in mammals. In addition, we found that the conserved hydrophobic amino acids in the 2-3 loop of Orai1 are important for the oligomerization and gating of channels and are regulated via an intramolecular interaction mechanism mediated by the N and C termini of Orai1. This study identifies a previously unknown SOCE mechanism in C. elegans and suggests that, while the STIM-Orai interaction is conserved between invertebrates and mammals, the gating mechanism for Orai channels differs considerably.</P>
Epidemiology and disease characteristics of symptomatic choledocholithiasis in Sri Lanka
Waduthanthri Supun Lakmal De S,Ajith Aloka Pathirana,Thejana Kamil Wijerathne,Bawantha Dilshan Gamage,Buddhika Kemiya Dassanayake,Mohan Malith De Silva 한국간담췌외과학회 2019 Annals of hepato-biliary-pancreatic surgery Vol.23 No.1
Backgrounds/Aims: Published data on choledocholithiasis in Sri Lanka is scarce. This study was conducted to determine epidemiological, clinical and endoscopic characteristics of choledocholithiasis in Sri Lanka. Methods: This was a retrospective study of consecutive patients for a period of three years until April 2016. The sample included patients from many parts of the island. Patients were selected from the endoscopy database of the unit and the data were collected from the records of the patients. Results: A total of 253 patients were included in the study. The mean age of the patients was 53.6 years. Patients presented with obstructive jaundice (58.5%), cholangitis (25.3%), biliary colic or upper abdominal pain (14.2%) and acute biliary pancreatitis (1.8%). There were 26 (10.3%) post cholecystectomy patients. Concomitant gallbladder stones were found in 173 patients (68.4%). Juxta-papillary diverticula were found in 36 patients (14.2%). Twenty-one (8.3%) and nine patients (3.6%) were found to have choledochal cysts and common bile duct strictures, respectively. Stones were commonly found in the distal common bile duct (68.4%). A majority of the patients had a single stone (47.8%). In 209 patients (79.6%), the size of the largest stones measured between 0.5-1.5 cm. Conclusions: Choledocholithiasis is a disease affecting middle-aged population with predominance among females in Sri Lanka. Patients with symptomatic choledocholithiasis commonly present with obstructive jaundice. In the present study, most of the stones were formed in anatomically normal biliary systems. Stones were predominantly distal, single and measured 0.5-1.5 cm in size. The observed features were favorable features for successful endoscopic clearance. None of the patients included in the study had primary CBD stones according to the available criteria.