The epithelial Na^＋ channel （ENaC） consists of α, β, γ subunits. Its expression and function are regulated by aldosterone at multiple levels including transcription. ENaC plays a key role in Na^＋ homeostasis a...The epithelial Na^＋ channel （ENaC） consists of α, β, γ subunits. Its expression and function are regulated by aldosterone at multiple levels including transcription. ENaC plays a key role in Na^＋ homeostasis and blood pressure. Mutations in ENaC subunit genes result in hypertension or hypotension, depending on the nature of the mutations. Transcription of αENaC is considered as the rate-limiting step in the formation of functional ENaC. As an aldosterone target gene, αENaC is activated upon aldosterone- mineralocorticoid receptor binding to the cis-elements in the αENaC promoter, which is packed into chromatin. However, how aldosterone alters chromatin structure to induce changes in transcription is poorly understood. Studies by others and us suggest that Dot1a-Af9 complex represses αENaC by directly binding and regulating targeted histone H3 K79 hypermethylation at the specific subregions of αENaC promoter. Aldosterone decreases Dot1a-Af9 formation by impairing expression of Dot1a and Af9 and by inducing Sgk1, which, in turn, phosphorylates Af9 at S435 to weaken Dot1a-Af9 interaction. MR attenuates Dot1a-Af9 effect by competing with Dot1a for binding Af9. Af17 relieves repression by interfering with Dot1a-Af9 interaction and promoting Dot1a nuclear export. Af17^-/- mice exhibit defects in ENaC expression, renal Na^＋ retention, and blood pressure control. This review gives a brief summary of these novel fndings.展开更多
Objective To characterize a novel frameshift mutation of the epithelial sodium channel(ENaC)βsubunit in a Chinese family with clinical suspicion of Liddle syndrome.And to emphasize that genetic testing is a confirmat...Objective To characterize a novel frameshift mutation of the epithelial sodium channel(ENaC)βsubunit in a Chinese family with clinical suspicion of Liddle syndrome.And to emphasize that genetic testing is a confirmatory evidence of the diagnosis of Liddle syndrome.Methods DNA samples from the proband with early-onset,treatment-resistant hypertension and hypokalemia and 31 additional relatives were all sequenced for mutations in exon 13 of theβ-ENaC andγ-ENaC genes,using amplification by polymerase chain reaction and direct DNA sequencing.展开更多
目的检测自发性高血压大鼠(SHR)和Wistar大鼠的ENaCs在mRNA水平的表达差异,探讨机械敏感性离子(Mechanosensitive Ion Channels,MS)对动脉压力感受器重调的作用。方法SHR大鼠和Wistar大鼠各6只,分别取左侧颈动脉窦、主动脉弓,异硫氰酸胍...目的检测自发性高血压大鼠(SHR)和Wistar大鼠的ENaCs在mRNA水平的表达差异,探讨机械敏感性离子(Mechanosensitive Ion Channels,MS)对动脉压力感受器重调的作用。方法SHR大鼠和Wistar大鼠各6只,分别取左侧颈动脉窦、主动脉弓,异硫氰酸胍-酚氯仿法抽提总RNA。采用荧光定量PCR法,分别测定αENaC、βENaC、γENaC在各组织的相对表达水平。结果正常血压的Wistar大鼠ENaCs表达在主动脉弓和颈动脉窦区域相对定量较SHR组大鼠高,在颈动脉窦区域表现更明显。结论高血压状态下,ENaCs在压力感受器区域下调表达,提示压力敏感性离子通道在压力反射重调方面可能发挥着一定作用。展开更多
Objective To study the electrophysiological properties of sodium channels in the apical membrane of human nasal epithelial cells Method Nasal epithelial cells of human inferior turbinate from patients with obstru...Objective To study the electrophysiological properties of sodium channels in the apical membrane of human nasal epithelial cells Method Nasal epithelial cells of human inferior turbinate from patients with obstructive sleep apnea syndrome were cultured in serum free medium on collagen gel coated membranes at an air liquid interface and studied by a patch clamp technique Results In cell attached patches, a typical single channel current with a conductance of 21 09?pS and reversal potential of -50 96 were recorded The permeability ratio P Na /P K was more than 5 80 In the presence of 10 4 mmol/L amiloride in the pipette, the incidence of sodium channels decreased from 26 67% to 5 13% This revealed that a population of channels were inhibited by amiloride at a dose of 10 4 mmol/L Ca 2+ at dose of 10 3 mmol/L did not influence the incidence of sodium channels There was no obvious association between voltage and the open probability of the channels Conclusions Our results indicate that most Na + channels in cell attached patches of human nasal epithelial cells are amiloride sensitive and Na + selective Only a few channels are amiloride insensitive The channels were not activated by extracellular Ca 2+ and the open probability followed a voltage independent manner展开更多
基金Supported by National Institutes of Health Grant 2R01 DK080236 06A1
文摘The epithelial Na^＋ channel （ENaC） consists of α, β, γ subunits. Its expression and function are regulated by aldosterone at multiple levels including transcription. ENaC plays a key role in Na^＋ homeostasis and blood pressure. Mutations in ENaC subunit genes result in hypertension or hypotension, depending on the nature of the mutations. Transcription of αENaC is considered as the rate-limiting step in the formation of functional ENaC. As an aldosterone target gene, αENaC is activated upon aldosterone- mineralocorticoid receptor binding to the cis-elements in the αENaC promoter, which is packed into chromatin. However, how aldosterone alters chromatin structure to induce changes in transcription is poorly understood. Studies by others and us suggest that Dot1a-Af9 complex represses αENaC by directly binding and regulating targeted histone H3 K79 hypermethylation at the specific subregions of αENaC promoter. Aldosterone decreases Dot1a-Af9 formation by impairing expression of Dot1a and Af9 and by inducing Sgk1, which, in turn, phosphorylates Af9 at S435 to weaken Dot1a-Af9 interaction. MR attenuates Dot1a-Af9 effect by competing with Dot1a for binding Af9. Af17 relieves repression by interfering with Dot1a-Af9 interaction and promoting Dot1a nuclear export. Af17^-/- mice exhibit defects in ENaC expression, renal Na^＋ retention, and blood pressure control. This review gives a brief summary of these novel fndings.
文摘Objective To characterize a novel frameshift mutation of the epithelial sodium channel(ENaC)βsubunit in a Chinese family with clinical suspicion of Liddle syndrome.And to emphasize that genetic testing is a confirmatory evidence of the diagnosis of Liddle syndrome.Methods DNA samples from the proband with early-onset,treatment-resistant hypertension and hypokalemia and 31 additional relatives were all sequenced for mutations in exon 13 of theβ-ENaC andγ-ENaC genes,using amplification by polymerase chain reaction and direct DNA sequencing.
文摘目的检测自发性高血压大鼠(SHR)和Wistar大鼠的ENaCs在mRNA水平的表达差异,探讨机械敏感性离子(Mechanosensitive Ion Channels,MS)对动脉压力感受器重调的作用。方法SHR大鼠和Wistar大鼠各6只,分别取左侧颈动脉窦、主动脉弓,异硫氰酸胍-酚氯仿法抽提总RNA。采用荧光定量PCR法,分别测定αENaC、βENaC、γENaC在各组织的相对表达水平。结果正常血压的Wistar大鼠ENaCs表达在主动脉弓和颈动脉窦区域相对定量较SHR组大鼠高,在颈动脉窦区域表现更明显。结论高血压状态下,ENaCs在压力感受器区域下调表达,提示压力敏感性离子通道在压力反射重调方面可能发挥着一定作用。
文摘Objective To study the electrophysiological properties of sodium channels in the apical membrane of human nasal epithelial cells Method Nasal epithelial cells of human inferior turbinate from patients with obstructive sleep apnea syndrome were cultured in serum free medium on collagen gel coated membranes at an air liquid interface and studied by a patch clamp technique Results In cell attached patches, a typical single channel current with a conductance of 21 09?pS and reversal potential of -50 96 were recorded The permeability ratio P Na /P K was more than 5 80 In the presence of 10 4 mmol/L amiloride in the pipette, the incidence of sodium channels decreased from 26 67% to 5 13% This revealed that a population of channels were inhibited by amiloride at a dose of 10 4 mmol/L Ca 2+ at dose of 10 3 mmol/L did not influence the incidence of sodium channels There was no obvious association between voltage and the open probability of the channels Conclusions Our results indicate that most Na + channels in cell attached patches of human nasal epithelial cells are amiloride sensitive and Na + selective Only a few channels are amiloride insensitive The channels were not activated by extracellular Ca 2+ and the open probability followed a voltage independent manner
