异丙酚对人动脉平滑肌细胞膜大电导钙激活钾通道的影响

异丙酚引起低血压的电生理机制有两种可能，一种可能是抑制交感神经肌接头活动，降低血浆儿茶酚胺的浓度，从而降低血管外周阻力；另一种可能是对内皮的影响和对血管平滑肌细胞的直接作用，Wanersted等在器官水平上证实了异丙酚扩张血管可能与大电导钙激活钾通道（BKCa）有关。本研究拟观察不同浓度异丙酚对人肠系膜动脉血管平滑肌细胞膜BKCa的影响，从分子水平探讨其扩张血管的机制。     

羟丁酸钠对大电导钙激活钾通道的作用

目的:应用膜片钳技术研究羟丁酸钠对新生鼠海马锥体神经元大电导钙激活钾通道的作用。方法:实验选用培养3～7天的锥体神经细胞。在对称性高钾溶液中(140mM),应用细胞贴附式和内面向外式膜片记录单通道电流。结果:(1)该通道电导为190pS左右,随着细胞内钙离子浓度的增加,通道开放概率明显增加,当膜内侧加入钾通道阻断剂TEA后通道活动被阻断;(2)在细胞贴附式膜片下,随着羟丁酸钠浓度的增加,通道开放概率和平均开放时间逐渐增加(P<0.05)。结论:说明羟丁酸钠对该通道具有明显的激活作用。这种激活作用可能与羟丁酸钠发挥全麻作用的分子机制有关。     

氯胺酮对海马神经细胞大电导钙激活钾通道的作用

目的:研究氯胺酮对海马神经细胞大电导钙激活钾(BK)通道的作用。方法:将培养的神经元置于对称性高钾溶液中,应用膜片钳技术,记录其单通道电流。用循环灌流的方法,观察了不同浓度氯胺酮对BK通道的作用。结果:(1)应用内面向外式膜片,该通道电导为170pS左右,随着胞内钙离子浓度的增加,通道开放概率明显增加(P<0.05),当膜内侧加入钾通道阻断剂(TEA)后,通道活动被阻断;(2)应用细胞贴附式膜片,当浴液内氯胺酮浓度为0.01～0.20mmol/L时,通道开放概率及电流幅值均降低(P<0.05);当其浓度为0.50～1.00mmol/L时,通道开放概率增加(P<0.05),而电流幅值与加药前相比无明显变化(P<0.05)。结论:氯胺酮对BK通道具有双向作用,其抑制作用可能是发挥麻醉效用时产生不良反应的原因之一,而其激活作用可能与全麻作用的分子机制有关。     

瑞芬太尼对人肠系膜小动脉平滑肌细胞大电导钙激活钾通道的影响

目的 观察瑞芬太尼对人肠系膜小动脉平滑肌细胞大电导钙激活钾通道(BKCa)的影响,探讨其扩张血管的机制.方法 酶消化法急性分离人肠系膜小动脉平滑肌细胞,采用全细胞膜片钳技术,+80 mV钳制电压下记录不同浓度瑞芬太尼(1.2、4.8、19.4、77.4和310.0 nmol/L)给药后人肠系膜小动脉平滑肌细胞BKCa电流及达峰时间,计算BKCa激活率.结果 瑞芬太尼可激活BKCa,使电流密度-电压曲线上移,激活电压不变;随瑞芬太尼浓度升高,BKCa激活率逐渐升高(P＜0.01),19.4 nmol/L时BKCa激活率趋于稳定;各浓度瑞芬太尼给药后BKCa电流达峰时间比较差异无统计学意义(P＞0.05);瑞芬太尼浓度与BKCa激活率成对数曲线关系,其半数最大激活效应浓度为(118±7)nmol/L.结论 瑞芬太尼浓度依赖性地激活人肠系膜小动脉平滑肌细胞BKCa,该作用可能是其产生扩张血管作用的机制.     

钙激活钾通道与逼尿肌功能调节

逼尿肌中的钙激活钾通道主要有大电导BKca和小电导Skca两类。反馈抑制细胞的钙内流，参与逼尿肌细胞的电位和收缩的稳态调节作用。本文综述了近年来这两类钙激活钾通道调节机制和作用的研究进展，及其在逼尿肌不稳定治疗中的应用前景。     

依托咪酯对鼠皮质神经元大电导钙激活性钾通道的作用

依托咪酯对鼠皮质神经元大电导钙激活性钾通道的作用李明星王泉云曾晓荣作者单位：６１００４１成都市，华西医科大学附属一院〔李明星（现在上海市第一肺科医院麻醉科）、王泉云、曾晓荣〕采用膜片钳技术的吸附式构型和内面向外式构型，实验了依托咪酯对体外培养ＳＤ新生...     

钙激活钾通道与逼尿肌功能调节

逼尿肌中的钙激活钾通道主要有大电导BKca和小电导Skca两类 ,反馈抑制细胞的钙内流 ,参与逼尿肌细胞的电位和收缩的稳态调节作用。本文综述了近年来这两类钙激活钾通道调节机制和作用的研究进展 ,及其在逼尿肌不稳定治疗中的应用前景。     

ATP敏感性钾通道与心肌保护

ATP敏感性钾通道(KATP)可调节细胞对组织缺血、缺氧的耐受性,介导并参与细胞或组织的保护作用。本文介绍KATP通道及其与心肌保护之间的关系。     

ATP敏感性钾通道与心肌保护

ATP敏感性钾通道（KATP）可调节细胞对组织缺血、缺氧的耐受性，介导并参与细胞或组织的保护作用。本文介绍KATP通道及其与心肌保护之间的关系。     

蛋白酪氨酸磷酸酶-3通过诱导肿瘤性巨噬细胞钙离子依赖性钾离子通道表达增强LoVo细胞侵袭性

目的 观察结肠癌肿瘤微环境中肿瘤细胞与巨噬细胞(M2)相互作用及对肿瘤细胞功能学的改变.方法 将转入蛋白酪氨酸磷酸酶-3(PRL-3)的LoVo细胞和M2细胞模拟肿瘤微环境进行共培养,通过Western blot检测M2细胞钙离子依赖性钾离子通道(KCNN4)蛋白表达,并检测LoVo细胞侵袭性的改变.结果 Western blot检测示PRL-3能通过共培养后诱导M2细胞KCNN4蛋白表达升高,而未作共培养的M2细胞KCNN4蛋白表达未升高.此外,经过共培养后LoVo细胞侵袭性升高(3367±135比1442±89,P＜0.05),而在阻断KCNN4蛋白表达后,LoVo细胞侵袭性降低(1388 ±87比2893±163,P＜0.05).结论 PRL-3在结肠癌肿瘤微环境中通过提高KCNN4表达从而增强LoVo细胞的侵袭性.     

Muscarinic M2 receptors inhibit Ca2+-activated K+ channels in rat bladder smooth muscle.

PURPOSE: To clarify the functional relationship between M2 muscarinic receptor and Ca2+-activated K+ channel, we investigated the effect of carbachol (CCh) on the membrane current of rat bladder smooth muscle cells. METHODS: Rat bladder single smooth muscle cells were patch clamped with whole-cell configuration. RESULTS: CCh (10 micro mol/L) transiently induced an outward current in the presence of K+ in the pipette solution. A high Ca2+ concentration in the pipette solution persistently induced an outward current, which was inhibited by CCh. In the presence of M2 inhibitor, AFDX-384, CCh induced the outward current persistently, indicating that M2 was involved in the current inhibition. In pertussis toxin pretreated cells, CCh did not apparently inhibit the outward current. The CCh-induced outward current was inhibited by iberiotoxin, a selective inhibitor of large-conductance Ca2+-activated K+ channels (BKCa). CONCLUSION: CCh induces BKCa, which is inhibited by M2- and Gi-mediated signal transduction pathway. This M2-mediated pathway may enhance contraction which is initiated by M3-stimulation in rat bladder smooth muscle.     

Activation of the Ca2+-Activated K+ Channel via Protein Kinase A-Dependent Phosphorylation in Human Prostatic Smooth Muscle Cells

Background: We investigated the functional importance of the Ca²⁺-activated K⁺ channel (K_Ca-channel) of human prostatic smooth muscle cells in cyclic adenosine 3', 5'-monophosphate (cAMP)-induced relaxation, to clarify signal transduction pathways and intracellular mechanisms of relaxation in prostatic smooth muscle.
Methods: Using the patch-clamp technique, we characterized the K_Ca-channel of cultured human prostatic smooth muscle cells. We also investigated the effects on the K_Ca-channels of forskolin, an activator of adenylate cyclase, amrinone, a phosphodiesterase inhibitor, and protein kinase A (A-kinase)-dependent phosphorylation.
Results: Single-channel current recordings from cultured human prostatic smooth muscle cells revealed the presence of K_Ca-channels (conductance 296.7±5.67 pS, n = 7). In cell-attached patch configurations, the K_Ca-channel was activated by forskolin (1CH mol/L) and amrinone (10⁻⁴ mol/L). In inside-out patch configurations, it was activated by catalytic subunits of A-kinase (10 U/mL).
Conclusions: We conclude that the K_Ca-channel of human prostatic smooth muscle cells is regulated by intracellular cAMP levels and that A-kinase mediates the cAMP-induced activation of the K_Ca-channel. This regulation of the K_Ca-channel by cAMP may at least partially explain cAMP-induced prostatic smooth muscle relaxation and the effectiveness of certain drugs for treatment of obstruction in benign prostatic hyperplasia.     

BKCa和PKG在氯胺酮舒张哮喘大鼠离体气管平滑肌中的作用

目的 评价大电导钙激活钾通道(BKCa)和蛋白激酶G(PKG)在氯胺酮舒张哮喘大鼠离体气管平滑肌中的作用.方法 健康SD大鼠,体重250 ～ 300 g,采用卵蛋白致敏法建立哮喘模型,取哮喘大鼠15只,每只大鼠制备2～3条离体气管环.取哮喘大鼠离体气管环36条,采用随机数字表法,将其分为3组(n=12):氯胺酮处理组(AK组)、BKCa阻断剂IBTX+氯胺酮处理组(AKI组)和PKG抑制剂KT-58232+氯胺酮处理组(AKK组);AK组采用0.1 mmol/L乙酰胆碱预收缩大鼠气管环达稳态后,用0.4 g/L氯胺酮孵育15 min; AKI组用乙酰胆碱和氯胺酮孵育前,用3 μmol/L IBTX孵育30 min;AKK组用入乙酰胆碱和氯胺酮孵育前,用2μmol/L KT-5823孵育30 min;采用气管环相连的力-位移换能器测定气管环舒张幅度.结果 与AK组比较,AKI组和AKK组大鼠离体气管平滑肌舒张幅度降低(P＜0.05).结论 氯胺酮可通过激活BKCa和PKG信号通路舒张哮喘大鼠离体气管平滑肌.     

A description of Ca2+ channels in human detrusor smooth muscle

OBJECTIVE: To characterize the Ca2+ channels in human detrusor smooth muscle and to investigate their contribution to spontaneous electrical activity. MATERIALS AND METHODS: Isolated human detrusor smooth muscle myocytes were used to measure ionic currents under voltage-clamp or membrane potential under current-clamp. Membrane potential oscillations were analysed in terms of oscillation frequency and amplitude using fast Fourier transforms. RESULTS: Under voltage-clamp an inward current dependent on extracellular Ca2+ was recorded using Cs+-filled patch electrodes. The current could be separated into two components on the basis of their sensitivity to Ni2+, verapamil or nicardipine, and their dependence on holding and clamp potential. A Ni2+-sensitive component activated over a relatively negative range of potentials (-60 to -20 mV) comprised about a third of the total current and was designated a T-type Ca2+ current. A verapamil/nicardipine-sensitive component, activated at more positive potentials, was designated an l-type Ca2+ current. Using K+-based filling solutions spontaneous transient outward currents were recorded that had the characteristics of current flow through BK channels. Membrane potential oscillations, under current-clamp increased in frequency but not amplitude as the mean membrane potential was made less negative. The voltage-dependence of oscillation frequency was similar to that of the l-type, but not T-type, Ca2+ current activation curve. Furthermore oscillation frequency was slowed by verapamil but not Ni2+. CONCLUSION: The study showed, for the first time, the presence of both T- and L-type Ca2+ channels in human detrusor smooth muscle; we propose a role for these channels in spontaneous activity. The results suggest that the L-type Ca2+ current can control membrane potential oscillation frequency. The significance of this finding for spontaneous contractions is discussed.     

脂多糖受体簇和大电导Ca2+活K+通道在脂多糖信号识别中的作用

背景 细菌脂多糖(lipopolysaccharide,LPS)可激活细胞合成和释放多种细胞因子,导致全身炎症反应.LPS识别及跨膜信号转导是引起细胞效应的关键,成为近年的研究热点.目的 对新近提出的“LPS受体簇”理论和大电导Ca2+激活K+通道(MaxiK)在LPS信号识别中的作用研究进展进行综述.内容 LPS与CD14结合后,不同的信号分子在脂质筏内聚集,LPS被释放到脂质双分子层,并与由多种受体分子组成的受体簇相互作用.根据不同的细胞类型和细菌刺激,形成了不同的LPS受体簇.MaxiK通道在LPS诱导的巨噬细胞信号转导过程的早期即被激活.并且以IκB-α/NF-κB为中心的促炎症反应依赖MaxiK的功能.趋向 需要进一步研究来阐明LPS受体簇在细胞膜特定区域内形成的确切分子机制,以及组成受体簇的几种蛋白分子在刺激识别和信号转导过程中的作用.