BK channels are widely expressed in both excitable and non-excitable cells and known to be involved in many physiological processes,such as vascular smooth tone regulation,neuronal firing and endocrine cell secretion[...BK channels are widely expressed in both excitable and non-excitable cells and known to be involved in many physiological processes,such as vascular smooth tone regulation,neuronal firing and endocrine cell secretion[1].Recently, the BK channels have展开更多
Large-conductance calcium-and voltage-dependent potassium(BK)channels are ubiquitously expressed in mammalian cells and participate in various physiological and pathological processes such as neurotransmission and cer...Large-conductance calcium-and voltage-dependent potassium(BK)channels are ubiquitously expressed in mammalian cells and participate in various physiological and pathological processes such as neurotransmission and cerebral ischemia.BK channels comprise up to four pore-formingαsubunits and zero to four accessory subunits.Although microglial BK currents were initially recorded 27 years ago,their roles have long been elusive.Studies have demonstrated that BK channels modulate the activation,phagocytosis,and probably migration of microglia and have associated microglial BK channels with many neurological diseases,including neuropathic pain and stroke.This review summarizes the available information regarding the biophysical,functional,and pathological aspects of microglial BK channels and discusses future directions of research into these channels.展开更多
A series of hydrazone and N-acylhydrazone derivatives of dehydroabietic acid were synthesized and evaluated for BK channel-opening activities in an assay system of CHO-K1 cells expressing hBKa channels.The assay resul...A series of hydrazone and N-acylhydrazone derivatives of dehydroabietic acid were synthesized and evaluated for BK channel-opening activities in an assay system of CHO-K1 cells expressing hBKa channels.The assay results indicated that the activities of the investigated compounds were influenced by the physicochemical properties of the substituent at hydrazone moiety.展开更多
Purpose: Large conductance, voltage- and Ca2+-activated K+ (BK) channel is thought to have a central role to regulate urinary bladder smooth muscle functions, and its dysfunction may lead to increase of urination freq...Purpose: Large conductance, voltage- and Ca2+-activated K+ (BK) channel is thought to have a central role to regulate urinary bladder smooth muscle functions, and its dysfunction may lead to increase of urination frequency and overactive bladder. The present study aims to investigate the expression pattern of BK channel subunits in the human urinary bladder, and how it changes in association with bladder outlet obstruction (BOO). Materials and Methods: Human bladders were obtained from 7 controls without prostatic enlargement and lower urinary tract symptoms and 4 BPH patients with clinically diagnosed overactive bladder who were verified by the International Prostate Symptom Score (IPSS) and prostate volume. The expression and location of BK channel protein complex was examined using immunohistochemistry with affinity-purified anti-BKα antibodies. A real-time RT-PCR was used to quantify the expression of each BK channel subunit (α and β1 - 4) gene in the mucosal and muscle layers of human urinary bladder. Results: Immunohistochemical staining for BK-α protein complex was localized in the muscle and submucosal regions of urinary bladder. RT-PCR analysis revealed the presence of α-, β1-, and β4-subunit genes of BK channel in the mucosal layer, α- and β1-subunit in the muscle layer. The expressions of α- and β1-subunit genes in the muscle (α: p = 0.0003, β1: p = 0.0003) and mucosal (α: p = 0.03, β1: p = 0.02) layers significantly decreased in BOO bladders compared with controls. The expression levels of α- and β1-subunit in mucosal layer were statistically correlated with storage score of IPSS (α;r = 0.84, p = 0.002, β1;r = 0.84, p = 0.002), and so were in muscle layer (α;r = 0.934, p 0.0001, β1;r = 0.917, p = 0.00018). Conclusions: BK channels, which are mainly composed of α- and β1-subunits, are expressed in both the mucosal and muscle layers of human urinary bladder. Decreased expression of BK channel in BOO might be implicated in the mechanisms underlying the development of overactive bladder.展开更多
基金supported by Natural Science Foundation of China grants10732070,10602031
文摘BK channels are widely expressed in both excitable and non-excitable cells and known to be involved in many physiological processes,such as vascular smooth tone regulation,neuronal firing and endocrine cell secretion[1].Recently, the BK channels have
基金Acknowledgments We thank Ms Mekie Takahashi, Ms Ritsuko Kanda （Nagaya University, Japan）, Dr Changliang Fu and Dr Shouqing Lu （Institute of Mechanics, Chinese Academy of Sciences） for technical assistance. This work was partly supported by research grants from the National Natural Science Foundation of China （10602031） and Grants-in-aid for Scientific Research on Priority Areas （#15086270 to M.S.） and Creative Research （# 16GS0308 to M.S.） from the Ministry of Education Science Sports and Culture, Japan.
基金National Natural Science Foundation of China(Grant No.31400924)the Priority Academic Program Development of the Jiangsu Higher Education Institutes(PAPD).
文摘Large-conductance calcium-and voltage-dependent potassium(BK)channels are ubiquitously expressed in mammalian cells and participate in various physiological and pathological processes such as neurotransmission and cerebral ischemia.BK channels comprise up to four pore-formingαsubunits and zero to four accessory subunits.Although microglial BK currents were initially recorded 27 years ago,their roles have long been elusive.Studies have demonstrated that BK channels modulate the activation,phagocytosis,and probably migration of microglia and have associated microglial BK channels with many neurological diseases,including neuropathic pain and stroke.This review summarizes the available information regarding the biophysical,functional,and pathological aspects of microglial BK channels and discusses future directions of research into these channels.
基金supports from the National Natural Science Foundation of China (Nos. 81202402 and 21272154)Shanghai Pujiang Program (No. 10PJ1403700)
文摘A series of hydrazone and N-acylhydrazone derivatives of dehydroabietic acid were synthesized and evaluated for BK channel-opening activities in an assay system of CHO-K1 cells expressing hBKa channels.The assay results indicated that the activities of the investigated compounds were influenced by the physicochemical properties of the substituent at hydrazone moiety.
文摘Purpose: Large conductance, voltage- and Ca2+-activated K+ (BK) channel is thought to have a central role to regulate urinary bladder smooth muscle functions, and its dysfunction may lead to increase of urination frequency and overactive bladder. The present study aims to investigate the expression pattern of BK channel subunits in the human urinary bladder, and how it changes in association with bladder outlet obstruction (BOO). Materials and Methods: Human bladders were obtained from 7 controls without prostatic enlargement and lower urinary tract symptoms and 4 BPH patients with clinically diagnosed overactive bladder who were verified by the International Prostate Symptom Score (IPSS) and prostate volume. The expression and location of BK channel protein complex was examined using immunohistochemistry with affinity-purified anti-BKα antibodies. A real-time RT-PCR was used to quantify the expression of each BK channel subunit (α and β1 - 4) gene in the mucosal and muscle layers of human urinary bladder. Results: Immunohistochemical staining for BK-α protein complex was localized in the muscle and submucosal regions of urinary bladder. RT-PCR analysis revealed the presence of α-, β1-, and β4-subunit genes of BK channel in the mucosal layer, α- and β1-subunit in the muscle layer. The expressions of α- and β1-subunit genes in the muscle (α: p = 0.0003, β1: p = 0.0003) and mucosal (α: p = 0.03, β1: p = 0.02) layers significantly decreased in BOO bladders compared with controls. The expression levels of α- and β1-subunit in mucosal layer were statistically correlated with storage score of IPSS (α;r = 0.84, p = 0.002, β1;r = 0.84, p = 0.002), and so were in muscle layer (α;r = 0.934, p 0.0001, β1;r = 0.917, p = 0.00018). Conclusions: BK channels, which are mainly composed of α- and β1-subunits, are expressed in both the mucosal and muscle layers of human urinary bladder. Decreased expression of BK channel in BOO might be implicated in the mechanisms underlying the development of overactive bladder.
