The liver has many significant functions,such as detoxification,the urea cycle,gluconeogenesis,and protein synthesis.Systemic diseases,hypoxia,infections,drugs,and toxins can easily affect the liver,which is extremely...The liver has many significant functions,such as detoxification,the urea cycle,gluconeogenesis,and protein synthesis.Systemic diseases,hypoxia,infections,drugs,and toxins can easily affect the liver,which is extremely sensitive to injury.Systemic infection of severe acute respiratory syndrome coronavirus 2 can cause liver damage.The primary regulator of intracellular pH in the liver is the Na+/H+exchanger(NHE).Physiologically,NHE protects hepatocytes from apoptosis by making the intracellular pH alkaline.Severe acute respiratory syndrome coronavirus 2 increases local angiotensin II levels by binding to angiotensinconverting enzyme 2.In severe cases of coronavirus disease 2019,high angiotensin II levels may cause NHE overstimulation and lipid accumulation in the liver.NHE overstimulation can lead to hepatocyte death.NHE overstimulation may trigger a cytokine storm by increasing proinflammatory cytokines in the liver.Since the release of proinflammatory cytokines such as interleukin-6 increases with NHE activation,the virus may indirectly cause an increase in fibrinogen and D-dimer levels.NHE overstimulation may cause thrombotic events and systemic damage by increasing fibrinogen levels and cytokine release.Also,NHE overstimulation causes an increase in the urea cycle while inhibiting vitamin D synthesis and gluconeogenesis in the liver.Increasing NHE3 activity leads to Na+loading,which impairs the containment and fluidity of bile acid.NHE overstimulation can change the gut microbiota composition by disrupting the structure and fluidity of bile acid,thus triggering systemic damage.Unlike other tissues,tumor necrosis factor-alpha and angiotensin II decrease NHE3 activity in the intestine.Thus,increased luminal Na+leads to diarrhea and cytokine release.Severe acute respiratory syndrome coronavirus 2-induced local and systemic damage can be improved by preventing virus-induced NHE overstimulation in the liver.展开更多
The Na^+/Ca^(2+) exchanger(NCX) protein family is a part of the cation/Ca^(2+) exchanger superfamily and participates in the regulation of cellular Ca^(2+) homeostasis. NCX1, the most important subtype in the NCX fami...The Na^+/Ca^(2+) exchanger(NCX) protein family is a part of the cation/Ca^(2+) exchanger superfamily and participates in the regulation of cellular Ca^(2+) homeostasis. NCX1, the most important subtype in the NCX family, is expressed widely in various organs and tissues in mammals and plays an especially important role in the physiological and pathological processes of nerves and the cardiovascular system. In the past few years, the function of NCX1 in the digestive system has received increasing attention; NCX1 not only participates in the healing process of gastric ulcer and gastric mucosal injury but also mediates the development of digestive cancer, acute pancreatitis, and intestinal absorption.This review aims to explore the roles of NCX1 in digestive system physiology and pathophysiology in order to guide clinical treatments.展开更多
Aim: To explore the possible mechanisms of male infertility caused by antisperm antibody (AsAb). Methods: Thesoluble interleukin-2 receptor (sIL-2R) level in serum was analyzed by ELISA and Na^+ -K^+ -exchanging ATPas...Aim: To explore the possible mechanisms of male infertility caused by antisperm antibody (AsAb). Methods: Thesoluble interleukin-2 receptor (sIL-2R) level in serum was analyzed by ELISA and Na^+ -K^+ -exchanging ATPase activi-ty in semen by phosphorus (Pi) assay. Results: The slL-2R level in serum was significantly higher and the Na^+ -K^+ -exchanging ATPase activity in semen significantly lower in AsAb positive infertile men when compared with thecontrols. Conclusion: The AsAb titer varies with the slL-2R level in serum. A decrease in Na^+ -K^+ -exchangingATPase activity in semen may play a role in male infertility caused by AsAb.展开更多
Objective Background and Objects: Naturally occurring temporal variability of action potentialduration (APD) in isolated myocytes has been noted. Most of the studies have beenfocusing on analyzes of the differences in...Objective Background and Objects: Naturally occurring temporal variability of action potentialduration (APD) in isolated myocytes has been noted. Most of the studies have beenfocusing on analyzes of the differences in ionic channels and currents among theepicardial-, mid-myocardial-(M) and endocardial myocytes, and the rate-dependent (adaptation) characteristics of APD. We have found that the change in APD during achange in frequency of stimulation mostly reflects a change in rate of repolarization at distinct membrane potential levels. We assumed that in the myocytes, there is balancing mechanism, which is constantly adjusting the various ionic currents accommodating to the changing conditions. This intrinsic ability of adaptation is important and may offer some of the consequences of the transmural heterogeneity in adaptation of APD. This adaptive behaviors maybe equally important in maintaining the normal electrophysiological properties and in induction of arrhythmia in a case of error in normal adaptation. Though most studies of Na +/Ca 2+ exchange (NCX) has been emphasized on its reverse activaty during pathyological condition. Our hypothesis is that reverse activaty of NCX also plays an important role in adjusting the repolarization of AP during a physiological condition. A mismatch between action potential (AP) repolarization and relaxation of the contraction can be caused by intracellular Ca 2+ transport abnormalities. Ca 2+ influx via reverse activation of NCX can load the sarcoplasmic recticulum (SR), which has arrhythmogenic effect.Methods We studied the single myocytes from the left ventricle of adult mongrel dogs. During the cell separation, collagenase was perfused through LAD by Langandorff system. We use the patch-clamp system to determinded AP in current clamp mode. Myocyte contraction was imaged by a video camera, shortening of unloaded myocytes was detected by a video edge motion detector, using changes in light intensity at the edges of the myocyte. Results From 60 consecutive recorded APs at a constant 1.0 Hz stimulation under steady state conditions we found there is a variance in the repolarization between 10mV and-40mV. We also found the variance in the APD during the rate adaptation range of repolarization. Fluctuation in the transient may contribute to the APD variability. To test thishypothesis we block the transient by intracellular dialysis with 10 mM EGTA(n=19), this caused a significant reduction in the coefficient variability (CV=SD/mean APD%) from 2.3± 0.8 to 1.3± 0.3 P< 0.01. During a rate change of the stimulation from 0.6 Hz to 1.0 Hz. The AP duration increased from 278±8 msec to 320±9 msec, Mean+SD, n=5, 50 APs, P< 0.05. contraction is accompanied by an after-contraction(A-CON). The relaxation of contraction precedes the repolarization of the AP. We assumed that the enhancement of repolarization and the production of after-contraction can be possibly induced by reverse mode of NCX. Reducing [Na +] o by substitution of 40mM Na + with Li + favors NCX activating the reverse mode, which significantly decreased the dome of the AP from 4.8± 0.3 to -10.6± 1.2mV, P< 0.05, and increased the APD from 330±13 to 368±14 msec. P< 0.05.Conclusions Intracellular calcium transient most likely contributes to the beat-to-beat variance of action potential duration in canine ventricular myocyte. And it attributes to the voltage-dependent switch of NCX mode. Calcium concentration is high inmyocytes during the repolarization, and high intracellular Ca 2+ activates NCX in such a manner, that it generates an inward (positive, depolarizing) current. This current works against the repolarization, it is prolonging it, with other words it increases the duration of the action potential. The magnitude of calcium concentration during repolarization is very much dependent on calcium transport in the SR. The calcium transport in the SR is subject to adrenergic actions, and other physiologic and pathologic regulators. Under pathologic conditions展开更多
We determined whether La3+ enter human peripheral blood lymphocytes via Na+/Ca2+ exchanger (measured with fura-2). We first compared the sensitivity of fura-2 with La3+ and Ca2+, the result indicates that the sensitiv...We determined whether La3+ enter human peripheral blood lymphocytes via Na+/Ca2+ exchanger (measured with fura-2). We first compared the sensitivity of fura-2 with La3+ and Ca2+, the result indicates that the sensitivity of fura-2 for La3+ is much greater than for Ca2+. La3+ forms a 1:1 La3+-fura-2 complex (apparent dissociation constant = 1.7x10(-12) mol/L, pH 7.05). Ouabain-pretreated cells, suspended in Na+-free medium, showed that La3+ can enter human lymphocytes via the Na-i(+)/Ca2+ (La3+)(o) exchanger and is found to be about 10(-12) mol/L in cells exposed to 0.4 mmol/L La3+. Otherwise, the higher concentration (0.1 mmol/L) blocks the Na-i(+)/Ca2+(La3+)(o) exchange-mediated influx of Ca2+, but the lower concentration (0.01 mmol/L) appears to increase Ca2+ entry.展开更多
To determine the effects of HOE 694, a new and potent Na＋- H＋ exchanger blocker, on transient inward current (Iti) and Na＋- Ca2＋ exchange during hypoxia- reoxygenation in guinea pig cardiomyocytes. Methods. Cardio...To determine the effects of HOE 694, a new and potent Na＋- H＋ exchanger blocker, on transient inward current (Iti) and Na＋- Ca2＋ exchange during hypoxia- reoxygenation in guinea pig cardiomyocytes. Methods. Cardiomyocytes were isolated from adult guinea pig ventricle. Experiment was performed in an experimental chamber that allowed the cells to be exposed to a sufficiently low O2 pressure. The cells were subjected to hypoxia and reoxygenation. The ionic currents were studied with patch clamp technique. Results. In the absence of HOE 694, hypoxia- reoxygenation induced Iti in 12 of 15 experiments; but in cardiomyocytes pretreated with HOE 694 (10～ 50μ mol/L), the incidence of Iti observed during reoxygenation was reduced to 5 of 11 experiments and 3 of 10 experiments, P Conclusions. Blockade of the Na＋- H＋ exchange by HOE 694 could reduce Ca2＋ overload upon hypoxia- reoxygenation, and inhibition of Na＋- H＋ exchange may also indirectly decrease Na＋- Ca2＋ exchange activity during hypoxia.展开更多
This paper reports the kinetic process of Ag ion exchange for the polycrystalline Na-β'-Al2O3.The interdiffusion coefficients in the process of Ag+ and Na+ ion exchange have been calculated with an 'one dimen...This paper reports the kinetic process of Ag ion exchange for the polycrystalline Na-β'-Al2O3.The interdiffusion coefficients in the process of Ag+ and Na+ ion exchange have been calculated with an 'one dimensional double side diffusion model'. Microstructures of the samples were observed and analysed by XRD, EMPA, SEM. The results of the conductivity measurements for samples with Na+, Ag+ and Na+-Ag+ mobile ions are presented and explained展开更多
文摘The liver has many significant functions,such as detoxification,the urea cycle,gluconeogenesis,and protein synthesis.Systemic diseases,hypoxia,infections,drugs,and toxins can easily affect the liver,which is extremely sensitive to injury.Systemic infection of severe acute respiratory syndrome coronavirus 2 can cause liver damage.The primary regulator of intracellular pH in the liver is the Na+/H+exchanger(NHE).Physiologically,NHE protects hepatocytes from apoptosis by making the intracellular pH alkaline.Severe acute respiratory syndrome coronavirus 2 increases local angiotensin II levels by binding to angiotensinconverting enzyme 2.In severe cases of coronavirus disease 2019,high angiotensin II levels may cause NHE overstimulation and lipid accumulation in the liver.NHE overstimulation can lead to hepatocyte death.NHE overstimulation may trigger a cytokine storm by increasing proinflammatory cytokines in the liver.Since the release of proinflammatory cytokines such as interleukin-6 increases with NHE activation,the virus may indirectly cause an increase in fibrinogen and D-dimer levels.NHE overstimulation may cause thrombotic events and systemic damage by increasing fibrinogen levels and cytokine release.Also,NHE overstimulation causes an increase in the urea cycle while inhibiting vitamin D synthesis and gluconeogenesis in the liver.Increasing NHE3 activity leads to Na+loading,which impairs the containment and fluidity of bile acid.NHE overstimulation can change the gut microbiota composition by disrupting the structure and fluidity of bile acid,thus triggering systemic damage.Unlike other tissues,tumor necrosis factor-alpha and angiotensin II decrease NHE3 activity in the intestine.Thus,increased luminal Na+leads to diarrhea and cytokine release.Severe acute respiratory syndrome coronavirus 2-induced local and systemic damage can be improved by preventing virus-induced NHE overstimulation in the liver.
基金Supported by the National Natural Science Foundation of China,No.816660412 to Xie R and No.81160265 to Xu JY
文摘The Na^+/Ca^(2+) exchanger(NCX) protein family is a part of the cation/Ca^(2+) exchanger superfamily and participates in the regulation of cellular Ca^(2+) homeostasis. NCX1, the most important subtype in the NCX family, is expressed widely in various organs and tissues in mammals and plays an especially important role in the physiological and pathological processes of nerves and the cardiovascular system. In the past few years, the function of NCX1 in the digestive system has received increasing attention; NCX1 not only participates in the healing process of gastric ulcer and gastric mucosal injury but also mediates the development of digestive cancer, acute pancreatitis, and intestinal absorption.This review aims to explore the roles of NCX1 in digestive system physiology and pathophysiology in order to guide clinical treatments.
文摘Aim: To explore the possible mechanisms of male infertility caused by antisperm antibody (AsAb). Methods: Thesoluble interleukin-2 receptor (sIL-2R) level in serum was analyzed by ELISA and Na^+ -K^+ -exchanging ATPase activi-ty in semen by phosphorus (Pi) assay. Results: The slL-2R level in serum was significantly higher and the Na^+ -K^+ -exchanging ATPase activity in semen significantly lower in AsAb positive infertile men when compared with thecontrols. Conclusion: The AsAb titer varies with the slL-2R level in serum. A decrease in Na^+ -K^+ -exchangingATPase activity in semen may play a role in male infertility caused by AsAb.
文摘Objective Background and Objects: Naturally occurring temporal variability of action potentialduration (APD) in isolated myocytes has been noted. Most of the studies have beenfocusing on analyzes of the differences in ionic channels and currents among theepicardial-, mid-myocardial-(M) and endocardial myocytes, and the rate-dependent (adaptation) characteristics of APD. We have found that the change in APD during achange in frequency of stimulation mostly reflects a change in rate of repolarization at distinct membrane potential levels. We assumed that in the myocytes, there is balancing mechanism, which is constantly adjusting the various ionic currents accommodating to the changing conditions. This intrinsic ability of adaptation is important and may offer some of the consequences of the transmural heterogeneity in adaptation of APD. This adaptive behaviors maybe equally important in maintaining the normal electrophysiological properties and in induction of arrhythmia in a case of error in normal adaptation. Though most studies of Na +/Ca 2+ exchange (NCX) has been emphasized on its reverse activaty during pathyological condition. Our hypothesis is that reverse activaty of NCX also plays an important role in adjusting the repolarization of AP during a physiological condition. A mismatch between action potential (AP) repolarization and relaxation of the contraction can be caused by intracellular Ca 2+ transport abnormalities. Ca 2+ influx via reverse activation of NCX can load the sarcoplasmic recticulum (SR), which has arrhythmogenic effect.Methods We studied the single myocytes from the left ventricle of adult mongrel dogs. During the cell separation, collagenase was perfused through LAD by Langandorff system. We use the patch-clamp system to determinded AP in current clamp mode. Myocyte contraction was imaged by a video camera, shortening of unloaded myocytes was detected by a video edge motion detector, using changes in light intensity at the edges of the myocyte. Results From 60 consecutive recorded APs at a constant 1.0 Hz stimulation under steady state conditions we found there is a variance in the repolarization between 10mV and-40mV. We also found the variance in the APD during the rate adaptation range of repolarization. Fluctuation in the transient may contribute to the APD variability. To test thishypothesis we block the transient by intracellular dialysis with 10 mM EGTA(n=19), this caused a significant reduction in the coefficient variability (CV=SD/mean APD%) from 2.3± 0.8 to 1.3± 0.3 P< 0.01. During a rate change of the stimulation from 0.6 Hz to 1.0 Hz. The AP duration increased from 278±8 msec to 320±9 msec, Mean+SD, n=5, 50 APs, P< 0.05. contraction is accompanied by an after-contraction(A-CON). The relaxation of contraction precedes the repolarization of the AP. We assumed that the enhancement of repolarization and the production of after-contraction can be possibly induced by reverse mode of NCX. Reducing [Na +] o by substitution of 40mM Na + with Li + favors NCX activating the reverse mode, which significantly decreased the dome of the AP from 4.8± 0.3 to -10.6± 1.2mV, P< 0.05, and increased the APD from 330±13 to 368±14 msec. P< 0.05.Conclusions Intracellular calcium transient most likely contributes to the beat-to-beat variance of action potential duration in canine ventricular myocyte. And it attributes to the voltage-dependent switch of NCX mode. Calcium concentration is high inmyocytes during the repolarization, and high intracellular Ca 2+ activates NCX in such a manner, that it generates an inward (positive, depolarizing) current. This current works against the repolarization, it is prolonging it, with other words it increases the duration of the action potential. The magnitude of calcium concentration during repolarization is very much dependent on calcium transport in the SR. The calcium transport in the SR is subject to adrenergic actions, and other physiologic and pathologic regulators. Under pathologic conditions
基金The authors acknowledge the support of the National Natural Scicnce Foundation of ChinaProvincial Natural Science Foundation of Shanxi.
文摘We determined whether La3+ enter human peripheral blood lymphocytes via Na+/Ca2+ exchanger (measured with fura-2). We first compared the sensitivity of fura-2 with La3+ and Ca2+, the result indicates that the sensitivity of fura-2 for La3+ is much greater than for Ca2+. La3+ forms a 1:1 La3+-fura-2 complex (apparent dissociation constant = 1.7x10(-12) mol/L, pH 7.05). Ouabain-pretreated cells, suspended in Na+-free medium, showed that La3+ can enter human lymphocytes via the Na-i(+)/Ca2+ (La3+)(o) exchanger and is found to be about 10(-12) mol/L in cells exposed to 0.4 mmol/L La3+. Otherwise, the higher concentration (0.1 mmol/L) blocks the Na-i(+)/Ca2+(La3+)(o) exchange-mediated influx of Ca2+, but the lower concentration (0.01 mmol/L) appears to increase Ca2+ entry.
基金This work was supported by Leading Specialty Funding of Shanghai, Grant No.94- III- 001.
文摘To determine the effects of HOE 694, a new and potent Na＋- H＋ exchanger blocker, on transient inward current (Iti) and Na＋- Ca2＋ exchange during hypoxia- reoxygenation in guinea pig cardiomyocytes. Methods. Cardiomyocytes were isolated from adult guinea pig ventricle. Experiment was performed in an experimental chamber that allowed the cells to be exposed to a sufficiently low O2 pressure. The cells were subjected to hypoxia and reoxygenation. The ionic currents were studied with patch clamp technique. Results. In the absence of HOE 694, hypoxia- reoxygenation induced Iti in 12 of 15 experiments; but in cardiomyocytes pretreated with HOE 694 (10～ 50μ mol/L), the incidence of Iti observed during reoxygenation was reduced to 5 of 11 experiments and 3 of 10 experiments, P Conclusions. Blockade of the Na＋- H＋ exchange by HOE 694 could reduce Ca2＋ overload upon hypoxia- reoxygenation, and inhibition of Na＋- H＋ exchange may also indirectly decrease Na＋- Ca2＋ exchange activity during hypoxia.
文摘This paper reports the kinetic process of Ag ion exchange for the polycrystalline Na-β'-Al2O3.The interdiffusion coefficients in the process of Ag+ and Na+ ion exchange have been calculated with an 'one dimensional double side diffusion model'. Microstructures of the samples were observed and analysed by XRD, EMPA, SEM. The results of the conductivity measurements for samples with Na+, Ag+ and Na+-Ag+ mobile ions are presented and explained
