四周模拟失重大鼠后身动脉平滑肌细胞钾电流的改变

本文采用全细胞膜片钳方法观察4周尾部悬吊大鼠（tail-suspended rats,SUS)隐动脉及肠系膜的动脉第2-6级动脉分支血管平滑肌细胞（vascular smooth muscle cells,VSMCs)钾电流密度的变化,结果表明：SUS大鼠后身动脉VSMCs的静息电位（RP）较对照大鼠（CON）后身动脉VSMCs的RP更负,SUS组隐动脉和肠系膜小鼠后身动脉VSMCs的静息电位（RP）较对照大鼠（CON）后身动脉VSMCs的RP更负,SUS组隐动脉和肠系膜小动脉VSMCs的全细胞钾电流密度较CON组显著增加,其中,SUS组的隐动脉和肠系膜小动脉VSMCs的大电导钙激活钙离子通道（BKca)和电压激活钾离子通道（Kv)电流密度较CON组的BKca和Kv电流密度均显著增加,以上结果提示,VSMCs的超极化及进一步引起的通过电压依赖性钙离子通道的钙内流减少可能是模拟失重引起后身动脉反应性降低的电生理机制之一。     

短期模拟失重可增强大鼠脑动脉平滑肌细胞L-型Ca~(2+)通道对血管紧张素Ⅱ的反应性

已有研究表明模拟失重可引起大鼠脑动脉发生区域特异性变化,其中Ca2+通道和肾素-血管紧张素系统(renin-angio-tensin system,RAS)可能发挥着重要的作用。本研究旨在探讨血管紧张素Ⅱ(angiotensin Ⅱ,Ang Ⅱ)对短期模拟失重大鼠脑基底动脉血管平滑肌细胞(vascular smooth muscle cells,VSMCs)L-型Ca2+通道(L-type calcium channel,CaL)功能的影响。模拟失重(尾部悬吊)3d后,用木瓜蛋白酶法分离大鼠脑基底动脉VSMCs。采用全细胞膜片钳技术,以Ba2+作为载流子,测定CaL电流密度,然后观察Ang Ⅱ对该电流的影响。结果显示,模拟失重3d对大鼠脑基底动脉VSMCs的膜电容和接入电阻无明显影响,但可致VSMCs的CaL电流密度显著增加。不过,模拟失重对CaL的电压激活特性和稳态激活曲线亦无明显影响。对照组和模拟失重组大鼠脑基底动脉VSMCs的CaL电流密度在给予Ang Ⅱ处理后均显著增加,且模拟失重组的增加幅度显著大于对照组。以上结果提示,3d短期模拟失重即可引起大鼠脑动脉VSMCs的CaL发生适应性改变,且可导致其对...     

BKCa增龄变化及其与血压的相关性

目的：探讨大电导钙激活钾通道（BKCa,MaxiK）增龄变化及其与血压水平的关系。方法：选取雄性9、15、21、27、33周龄自发高血压大鼠（SHR）及对照组正常血压大鼠（WKY）,每周龄两类大鼠各4只;测定各周龄SHR和WKY的腹主动脉血压;分离肠系膜小动脉及其血管平滑肌细胞;利用膜片钳全细胞模式记录肠系膜小动脉VSMCs钾电流、用四乙胺（TEA）阻断BKCa后的电流、膜电容,以计算BKCa电流值、BKCa电流密度;探讨BKCa电流密度增龄变化与血压的关系。结果：SHR肠系膜小动脉血管平滑肌细胞（VSMCs）BKCa电流密度随增龄降低,而WKY随增龄的变化无统计学意义（P〉0．05）;SHR肠系膜小动脉VSMCs BKCa电流密度与腹主动脉MABP高度相关（r=-0．7174）,而WKY肠系膜小动脉VSMCs BKCa电流密度与腹主动脉MABP低度相关（r=-0．4832）。结论：BKCa电流和电流密度随增龄衰减,血压水平是衰减程度的重要反应;BKCa电流密度与血压水平高度相关。     

模拟失重增强大鼠脑动脉血管平滑肌细胞大电导钙激活钾通道功能

本工作旨在探讨短期模拟失重大鼠脑动脉血管平滑肌细胞（vascular smooth muscle cells,VSMCs）大电导钙激活钾通道（large conductance calcium-activated potassium channels,BKCa channels）功能的改变。以尾部悬吊大鼠模型模拟失重对脑血管的影响。应用激光扫描共聚焦显微镜测定VSMCs胞内游离钙浓度（[Ca^2＋]i）;采用细胞贴附模式,记录BKCa通道的单通道活动。结果表明,模拟失重1周后,大鼠脑动脉VSMCs的[Ca^2＋]i比对照组显著升高（P〈0．05）：BKCa通道的开放概率（Po）与平均开放时间（To）显著增加（P〈0．05）,而单通道电导与平均关闭时间（Tc）则无显著变化。总之,1周模拟失重可引起脑动脉VSMCs的BKCa通道功能显著增强,且与细胞[Ca^2＋]i的升高同步出现。结果提示,脑动脉VSMCs的离子通道机制可能参与介导模拟失重引起的脑血管适应性变化。     

SHRsp内脏阻力血管平滑肌钙通道动力学特征

用膜片箝全细胞钡电流方式比较成年雄性卒中易感型自发性高血压大鼠（ＳＨＲｓｐ）及正常大鼠（Ｗｉｓｔａｒ）肠系膜动脉Ａ４－Ａ５分支阻力血管平滑肌电压依赖性钙通道的动力学特性。结果发现：１）两种大鼠该段均存在有Ｌ型与Ｔ型钙通道。２）峰值电流（ｐｅａｋＩＢａ２＋）幅度和密度ＳＨＲｓｐ均大于Ｗｉｓｔａｒ大鼠。３）通道激活时间常数（τａ）ＳＨＲｓｐ小于Ｗｉｓｔａｒ大鼠,失活时间常数（τｉ）于箝制电压（ＨＰ）＝－４０ｍＶ时,两种大鼠无区别,ＨＰ＝－８０ｍＶ时,ＳＨＲｓｐ显著大于Ｗｉｓｔａｒ。４）和Ｗｉｓｔａｒ大鼠相比较,ＳＨＲｓｐ的稳态激活曲线（Ｄ∞）与稳态失活曲线（Ｆ∞）,均呈现左移。ＳＨＲｓｐ肠系膜动脉阻力血管平滑肌电压依赖性钙通道的如此特征更有利于胞外钙离子进入胞内。而关于内脏阻力血管的实验结果迄今鲜有报道。     

大鼠海马CA1区神经元Na~+通道在出生后早期发育的变化

为了探索大鼠海马CA1区锥体神经元电压门控性Na+通道发育的关键期,本研究采用膜片钳技术,分别对急性分离的出生后0周、1周、2周、3周、4周的大鼠海马CA1区锥体神经元进行全细胞记录。结果显示,随着大鼠出生后周龄的增大,Na+通道的最大电流密度逐渐增大,出生后1~4周相对于出生后0周的最大电流密度的增幅分别为(42.76±4.91)%、(146.80±7.63)%、(208.79±5.28)%、(253.72±5.74)%(n=10,P<0.05),出生后1周与2周之间的增幅最为显著;Na+通道的稳态激活曲线向左移动,出生后0~2周的半数激活电压逐渐减小,分别为39.06±0.65、43.41±0.52、48.29±0.45(mV,n=10,P<0.05),出生后2~4周的半数激活电压变化不大,出生后0~4周的斜率因子没有显著变化;Na+通道的稳态失活曲线及半数失活电压没有显著变化,但出生后1~2周斜率因子减小,分别为5.77±0.56、4.42±0.43(n=10,P<0.05),出生后0~1周、2~4周之间的斜率因子没有明显变化;Na+通道失活后恢复曲线左移,出生后1~3周的恢复时间常数逐渐减小,分别为8.30±0.24、7.15±0.21、6.18±0.25(ms,n=10,P<0.05),而出生后0~1周、3~4周之间没有明显变化;随着出生后的发育,海马CA1区锥体神经元动作电位发生变化,超射值与最大上升速率增大,阈值降低,与Na+电流的变化一致。结果提示,出生后1~2周可能是电压门控性Na+通道发育的关键期,此期间Na+通道分布显著增加,激活曲线左移,失活速度变快,失活后恢复的时间缩短。     

血管钠肽对大鼠肠系膜动脉平滑肌细胞Ca2+激活K+通道的作用

目的研究血管钠肽(VNP)对大鼠肠系膜动脉血管平滑肌细胞(VSMCs)Ca2+激活K+通道(Kca)的作用及其机制.方法采用全细胞膜片钳技术观察VNP对Kca的影响,以及HS-142-1、8-Br-cGMP和美蓝(MB)在这一过程中的作用.结果①VNP(10-6 mol/L)显著增强Kca(P＜0.05,n=5).②8-Br-CGMP(10-3mol/L)模拟VNP增强Kca的作用(P＜0.05,n=6).③HS-142-1(2×10-5mol/L)或MB(10-5mol/L)完全阻断VNP增加Kca电流密度的作用.结论VNP通过作用于VSMCs的钠尿肽GC耦联受体,升高细胞内的cGMP水平,激活Kca.     

不同年龄大鼠心肌细胞瞬时外向钾电流的变化

本文旨在研究心肌细胞瞬时外向钾电流(transient outward potassium current,Ito)的随龄变化及其药物反应性改变。Sprague Dawley大鼠28只,分为青年组(3~5月龄)、成年组(13~15月龄)和老年组(22~24月龄)。酶法分离心室肌细胞,应用全细胞膜片钳技术记录各组Ito。并于细胞外液分别加入1.0μmol/L异丙肾上腺素和2.0mmol/L4-氨基吡啶干预,观察Ito的变化。结果显示,与青年组和成年组相比,老年组Ito电流密度显著增加。门控动力学研究显示,老年组Ito电流稳态激活曲线左移,通道关闭态失活速率明显降低,稳态失活后恢复速率加快,而稳态失活过程无明显变化。老年组Ito对选择性抑制剂4-氨基吡啶的反应性与青年组和成年组相似,但老年组Ito对β受体激动剂异丙肾上腺素的反应性却明显弱于青年组和成年组,各组电流密度分别增加55.9%、127.5%和125.8%。上述结果提示,随着大鼠年龄的增加,心肌细胞Ito电流密度显著升高,与通道门控的激活、关闭态失活和失活后恢复机制改变有关,且老年鼠Ito对异丙肾上腺素的反应性降低。     

慢性阻断血管紧张素Ⅱ1型受体不能完全防止模拟失重大鼠血管的适应性结构变化

我们以前的工作提示,在模拟失重所引起的血管区域特异性适应变化中,局部肾素．血管紧张素系统（local reninangiotensin system,L-RAS）可能发挥关键调控作用。本文以losartan慢性阻断血管紧张素Ⅱ1型受体（angiotensin Ⅱtypelreceptor,AT1R）,观察模拟失重是否仍能引起血管的这种适应性改变,并检测大血管管壁L-RAS主要成分的表达是否也发生相应变化。以尾部悬吊大鼠模型模拟失重的生理影响。制作基底动脉、胫前动脉、颈总动脉和腹主动脉的HE染色切片,在光学显微镜下进行形态观测：用免疫组织化学技米测量颈总动脉和腹主动脉壁的血管紧张素原（angiotensinogen,AGT）及AT-R的表达变化。结果表明：4周模拟失重引起大鼠基底动脉中膜和颈总动脉管壁各平滑肌肌层肥厚,而胫前动脉和腹主动脉则发生萎缩性改变;给予losartan4周引起上述4种血管皆发生萎缩性变化;阻断AT1R,模拟失重仍然能引起基底动脉、颈总动脉发生相对肥厚性改变和腹主动脉萎缩加重。4周模拟失重还引起颈总动脉壁中AGT和AT1R表达上调,而腹主动脉壁及血管周围组织中AGT和AT1R表达下调;给予losartan4周仅引起腹主动脉壁中AGT和AT1R表达减少;阻断AT1R,模拟失重使腹主动脉壁AT1R表达进一步减少。结果提示,4周模拟失重引起大鼠脑、颈部与后身大、中动脉血管的形态结构改变和L-RAS主要成分表达发生上调或下调,血管L-RAS在其中可能发挥关键性调控作用;但在慢性阻断AT1R的条件下,其它调控机制仍可能在脑血管适应性调节中发挥一定作用。     

大鼠海马CA1区锥体神经元I_A和I_K在出生后早期的变化

大脑快速发育期(brain growth spurt,BGS)是神经元生长、突触连接的关键时期;电压门控性K+通道是维持细胞兴奋性和神经元间信息传递的关键通道。本文旨在探究BGS期内大鼠海马CA1区锥体神经元电压门控性K+通道电流及其通道动力学特性的变化,以期找出大鼠海马CA1区锥体神经元电压门控性K+通道发育的关键期。采用全细胞膜片钳技术,研究出生后0~4周大鼠海马CA1区脑片上的锥体神经元全细胞电压门控性K+通道电流及其通道动力学特性。结果显示:在测试电压为+90mV下,以出生后0周为参照,出生后1~4周的瞬时外向K+通道电流(IA)的最大电流密度的增幅分别为(16.14±0.51)%、(81.73±10.71)%、(106.72±5.29)%、(134.58±8.81)%(n=10,P<0.05);延迟整流K+通道电流(IK)的最大电流密度增幅分别为(16.75±3.88)%、(134.01±2.85)%、(180.56±8.49)%、(194.5±8.53)%(n=10,P<0.05),显示K+通道电流密度于1~2周增幅最大;IA的激活曲线向左移,半数激活电压随周龄增加逐渐减小,分别为14.67±0.75、13.46±0.64、8.39±0.87、4.60±0.96、0.54±0.92(mV,n=10,P<0.05);IK的激活曲线向左移,半数激活电压随周龄增加逐渐减小,分别为8.94±0.85、6.65±0.89、0.47±1.15、1.80±0.89、8.56±1.08(mV,n=10,P<0.05)。IA的失活曲线向左移,0周龄与1周龄之间的半数失活电压没有显著性差异,而出生后1~4周随周龄增加半数失活电压逐渐减小(P<0.05),分别为45.68±1.26、46.81±0.78、48.64±0.81、51.96±1.02、58.31±1.35(mV,n=10)。以上结果表明,随着鼠龄的增加,IA和IK电流密度逐渐增加,电压门控性K+通道半数激活、失活电压降低,尤其是出生后1周至2周变化明显,上述变化与海马神经元的逐渐发育成熟及其功能的完善有关。     

Short-term simulated weightlessness enhances response of L-type calcium channel to angiotensin II in cerebral vascular smooth muscle cells in rats

Some studies suggest that the calcium channels and rennin-angiotensin system (RAS) play pivotal roles in the region-specific vascular adaptation due to simulated weightlessness. This study was designed to clarify if angiotensin II (Ang II) was involved in the adaptational change of the L-type calcium channel (Ca(L)) in the cerebral arterial vascular smooth muscle cells (VSMCs) under simulated weightlessness. Tail suspension (SUS) for 3 d was used to simulate immediate early cardiovascular changes to weightlessness. Then VSMCs in cerebral basilar artery were enzymatically isolated using papain, and Ca(L) current (barium instead of calcium as current carrier) in VSMCs was measured by whole-cell patch-clamp techniques. The results showed that 3-day simulated weightlessness significantly increased current density of Ca(L). However, I-V relationships of normalized peak current densities and steady-state activation curves of Ca(L) were not affected by simulated weightlessness. Although Ang II significantly increased current densities of Ca(L) in both SUS and control rats, the increase of Ca(L) current density in SUS rats was much more than that in control rats. These results suggest that 3-day simulated weightlessness induces the adaptational change of Ca(L) in cerebral VSMCs including increased response to Ang II, indicating that Ang II may play an important role in the adaptational change of cerebral arteries under microgravity.     

Differential activation of potassium channels in cerebral and hindquarter arteries of rats during simulated microgravity

The purpose of this study was to test the hypothesis that differential autoregulation of cerebral and hindquarter arteries during simulated microgravity is mediated or modulated by differential activation of K(+) channels in vascular smooth muscle cells (VSMCs) of arteries in different anatomic regions. Sprague-Dawley rats were subjected to 1- and 4-wk tail suspension to simulate the cardiovascular deconditioning effect due to short- and medium-term microgravity. K(+) channel function of VSMCs was studied by pharmacological methods and patch-clamp techniques. Large-conductance Ca(2+)-activated K(+) (BK(Ca)) and voltage-gated K(+) (K(v)) currents were determined by subtracting the current recorded after applications of 1 mM tetraethylammonium (TEA) and 1 mM TEA + 3 mM 4-aminopyridine (4-AP), respectively, from that of before. For cerebral vessels, the normalized contractility of basilar arterial rings to TEA, a BK(Ca) blocker, and 4-AP, a K(v) blocker, was significantly decreased after 1- and 4-wk simulated microgravity, respectively. VSMCs isolated from the middle cerebral artery branches of suspended rats had a more depolarized membrane potential (E(m)) and a smaller K(+) current density compared with those of control rats. Furthermore, the reduced total current density was due to smaller BK(Ca) and smaller K(v) current density in cerebral VSMCs after 1- and 4-wk tail suspension, respectively. For hindquarter vessels, VSMCs isolated from second- to sixth-order small mesenteric arteries of both 1- and 4-wk suspended rats had a more negative E(m) and larger K(+) current densities for total, BK(Ca), and K(v) currents. These results indicate that differential activation of K(+) channels occur in cerebral and hindquarter VSMCs during short- and medium-term simulated microgravity. It is further suggested that different profiles of channel remodeling might occur in VSMCs as one of the important underlying cellular mechanisms to mediate and modulate differential vascular adaptation during microgravity.     

Differential regulation of L-type Ca2+ channels in cerebral and mesenteric arteries after simulated microgravity in rats and its intervention by standing

This study was designed to clarify whether simulated microgravity can induce differential changes in the current and protein expression of the L-type Ca(2+) channel (Ca(L)) in cerebral and mesenteric arteries and whether these changes can be prevented by daily short-duration -G(x) exposure. Tail suspension [hindlimb unloading (HU)] for 3 and 28 days was used to simulate short- and medium-term microgravity-induced deconditioning effects. Standing (STD) for 1 h/day was used to provide -G(x) as a countermeasure. Whole cell patch-clamp experiments revealed an increase in current density of Ca(L) of vascular smooth muscle cells (VSMCs) isolated from cerebral arteries of rats subjected to HU and a decrease in VSMCs from mesenteric arteries. Western blot analysis revealed a significant increase and decrease of Ca(L) channel protein expression in cerebral and small mesenteric arterial VSMCs, respectively, only after 28 days of HU. STD for 1 h/day did not prevent the increase of Ca(L) current density in cerebral arterial VSMCs, but it prevented completely (within 3 days) and partially (28 days) the decrease of Ca(L) current density in small mesenteric arterial VSMCs. Consistent with the changes in Ca(L) current, STD for 1 h/day did not prevent the increase of Ca(L) expression in cerebrovascular myocytes but did prevent the reduction of Ca(L) expression in mesenteric arterial VSMCs subjected to 28 days of HU. These data indicate that simulated microgravity up- and downregulates the current and expression of Ca(L) in cerebral and hindquarter VSMCs, respectively. STD for 1 h/day differentially counteracted the changes of Ca(L) function and expression in cerebral and hindquarter arterial VSMCs of HU rats, suggesting the complexity of the underlying mechanisms in the effectiveness of intermittent artificial gravity for prevention of postflight cardiovascular deconditioning, which needs further clarification.     

Differential regulation and recovery of intracellular Ca2+ in cerebral and small mesenteric arterial smooth muscle cells of simulated microgravity rat

Background

The differential adaptations of cerebrovasculature and small mesenteric arteries could be one of critical factors in postspaceflight orthostatic intolerance, but the cellular mechanisms remain unknown. We hypothesize that there is a differential regulation of intracellular Ca²⁺ determined by the alterations in the functions of plasma membrane Ca_L channels and ryanodine-sensitive Ca²⁺ releases from sarcoplasmic reticulum (SR) in cerebral and small mesenteric vascular smooth muscle cells (VSMCs) of simulated microgravity rats, respectively.

Methodology/Principal Findings

Sprague-Dawley rats were subjected to 28-day hindlimb unweighting to simulate microgravity. In addition, tail-suspended rats were submitted to a recovery period of 3 or 7 days after removal of suspension. The function of Ca_L channels was evaluated by patch clamp and Western blotting. The function of ryanodine-sensitive Ca²⁺ releases in response to caffeine were assessed by a laser confocal microscope. Our results indicated that simulated microgravity increased the functions of Ca_L channels and ryanodine-sensitive Ca²⁺ releases in cerebral VSMCs, whereas, simulated microgravity decreased the functions of Ca_L channels and ryanodine-sensitive Ca²⁺ releases in small mesenteric VSMCs. In addition, 3- or 7-day recovery after removal of suspension could restore the functions of Ca_L channels and ryanodine-sensitive Ca²⁺ releases to their control levels in cerebral and small mesenteric VSMCs, respectively.

Conclusions

The differential regulation of Ca_L channels and ryanodine-sensitive Ca²⁺ releases in cerebral and small mesenteric VSMCs may be responsible for the differential regulation of intracellular Ca²⁺, which leads to the altered autoregulation of cerebral vasculature and the inability to adequately elevate peripheral vascular resistance in postspaceflight orthostatic intolerance.     

Development of ionic currents of zebrafish slow and fast skeletal muscle fibers

Voltage-gated Na+ and K+ channels play key roles in the excitability of skeletal muscle fibers. In this study we investigated the steady-state and kinetic properties of voltage-gated Na+ and K+ currents of slow and fast skeletal muscle fibers in zebrafish ranging in age from 1 day postfertilization (dpf) to 4-6 dpf. The inner white (fast) fibers possess an A-type inactivating K+ current that increases in peak current density and accelerates its rise and decay times during development. As the muscle matured, the V50s of activation and inactivation of the A-type current became more depolarized, and then hyperpolarized again in older animals. The activation kinetics of the delayed outward K+ current in red (slow) fibers accelerated within the first week of development. The tail currents of the outward K+ currents were too small to allow an accurate determination of the V50s of activation. Red fibers did not show any evidence of inward Na+ currents; however, white fibers expressed Na+ currents that increased their peak current density, accelerated their inactivation kinetics, and hyperpolarized their V50 of inactivation during development. The action potentials of white fibers exhibited significant changes in the threshold voltage and the half width. These findings indicate that there are significant differences in the ionic current profiles between the red and white fibers and that a number of changes occur in the steady-state and kinetic properties of Na+ and K+ currents of developing zebrafish skeletal muscle fibers, with the most dramatic changes occurring around the end of the first day following egg fertilization.     

TTX-sensitive voltage-gated Na+ channels are expressed in mesenteric artery smooth muscle cells

The presence and properties of voltage-gated Na+ channels in mesenteric artery smooth muscle cells (SMCs) were studied using whole cell patch-clamp recording. SMCs from mouse and rat mesenteric arteries were enzymatically dissociated using two dissociation protocols with different enzyme combinations. Na+ and Ca2+ channel currents were present in myocytes isolated with collagenase and elastase. In contrast, Na+ currents were not detected, but Ca2+ currents were present in cells isolated with papain and collagenase. Ca2+ currents were blocked by nifedipine. The Na+ current was insensitive to nifedipine, sensitive to changes in the extracellular Na+ concentration, and blocked by tetrodotoxin with an IC50 at 4.3 nM. The Na+ conductance was half maximally activated at -16 mV, and steady-state inactivation was half-maximal at -53 mV. These values are similar to those reported in various SMC types. In the presence of 1 microM batrachotoxin, the Na+ conductance-voltage relationship was shifted by 27 mV in the hyperpolarizing direction, inactivation was almost completely eliminated, and the deactivation rate was decreased. The present study indicates that TTX-sensitive, voltage-gated Na+ channels are present in SMCs from the rat and mouse mesenteric artery. The presence of these channels in freshly isolated SMC depends critically on the enzymatic dissociation conditions. This could resolve controversy about the presence of Na+ channels in arterial smooth muscle.     

Role of Ba2+-resistant K+ channels in endothelium-dependent hyperpolarization of rat small mesenteric arteries

In rat small mesenteric arteries, the influence of modulation of basal smooth muscle K+ efflux on the mechanism of endothelium-dependent hyperpolarization was investigated. The membrane potentials of the vascular smooth muscle cells were measured using conventional microelectrode techniques. Incubation of resting arteries with the gap junction uncoupler carbenoxolone (20 micro M) decreased the endothelium-dependent hyperpolarization elicited by a submaximal concentration of acetylcholine (3 micro M) to about 65% of the control. In the presence of Ba2+ (200 micro M), which depolarized the membrane potential by 10 mV, the acetylcholine-induced membrane potential response was doubled in magnitude, reaching values not different from control. Moreover, the hyperpolarization was more resistant to carbenoxolone in these conditions. Finally, both in the absence and in the presence of carbenoxolone, the combined application of Ba2+ and ouabain (0.5 mM) did not abolish the acetylcholine response. These results suggest that gap junctional coupling plays a role in endothelium-dependent hyperpolarization of smooth muscle cells of resting rat small mesenteric arteries. Additionally, these findings show that the hyperpolarization does not rely on activation of inward rectifying K+ channels. Although a minor contribution of Na-K pumping cannot be excluded, the Ba2+ experiments show that the membrane electrical response is mediated by activation of a Ba2+-resistant K+ conductance.     

模拟失重大鼠心肌与血管组织的热应激诱导HSP70表达

为研究模拟失重是否可以引起大鼠心肌与血管组织HSP70的诱导表达发生改变,用尾部悬吊大鼠模型模拟失重,以研究失重对生理的影响,用Northern杂交与Western印迹分析检测4周模拟失重大鼠热应激后并在室温下恢复1h(SUS-H1)或2h(SUS-H2_心肌,血管组织HSP70表达的变化,结果表明,热应激后,各组大鼠心肌组织的HSP72 mRNA表达的均显著增加,但SUS－H2大鼠心肌组织的表达显著低于CON－H2组;各组大鼠心肌组织HSP72表达也均显著增加,但SUS－H1与SUS－H2大鼠的表达与相应对照组相比,则仅呈降低趋势,其底动脉血管组织的HSP72 mRNA与HSP72诱导表达均显著增高,而在股动脉则两者仅呈降低趋势,上述结果提示,模拟失重可导致大鼠心肌发生类似衰老的心肌改变;身体前,后部血管组织HSP70的诱导表达变化可能与血管的分化性适应方向一致。