刺五加叶皂甙单体Sb对培养大鼠心肌细胞动作电位的影响

本研究中所用的刺五加叶皂甙单体Ｓｂ（５０、２００μｇ／ｍＬ），使培养的ｗｉｓｔａｒ大鼠心肌细胞动作电位的波幅、波宽、阈电位、最大舒张电位、超射、最大除极速度及复极（１０％、５０％、９０％）水平的动作电位波宽一致减小。Ｃａ２＋８０μｇ／ｍＬ能使之反转，Ｓｂ作用与尼莫地平作用相似。上述结果表明Ｓｂ具有钙通道阻滞作用。     

The effect of racemic ketamine on the large conductance Ca-activated potassium (BK) channels in GH3 cells

Recently, inhalation anesthetics have been reported to block BK channels in adrenal chromaffin cells. To determine if BK block was characteristic only of inhalation anesthetics or was also a property of other general anesthetics we examined the effects of ketamine, an intravenous general anesthetic which is structurally different than inhalation anesthetics. Cell-attached and excised patch single channel and standard whole cell recording techniques were used to examine the effect of racemic ketamine on the BK channel activity in GH₃ cells. When solutions containing 150 mM KCl are used in both the pipette and bath, the BK channels are characterized as a voltage-dependent channel with a unit conductance of 150–300 pS. Racemic ketamine (at clinically relevant concentrations; 2–500 μM) selectively blocked BK channels in a dose-dependent, reversible manner as evidenced by decreases in NP_o (number of channels × open probability). This decrease was due to both a decrease in mean open time and an increase in the mean closed time but without a decrease in single-channel current amplitude. Ketamine shifts the P_o vs voltage curve to higher potentials without a change in the slope of the voltage dependence. Ketamine also shifts the P_o vs [Ca⁺²] relationship to higher Ca⁺² concentrations. The IC₅₀ for the single-channel block by ketamine is 20.3 ± 15.9 μM. In an effort to confirm that the effect of ketamine was predominantly due to a block of the BK channels, standard whole cell techniques were utilized. As with the single-channel experiments, ketamine (2–500 μM) produced a dose-dependent, voltage-independent and reversible decrease in outward current with an IC₅₀ of 23.7 ± 11.5 μM. Addition of 100 μM ketamine to cells pretreated with the BK channel blocker, charybdotoxin (ChTX), did not result in a further decrease in outward current. These results demonstrate a selective effect of ketamine at clinically relevant concentrations which is consistent with results reported for inhalation anesthetics.     

Activation of the langendorff perfused rat heart depolarized by increased external potassium concentration

Myocardial activation under depolarized conditions was studied in spontaneously beating Langendorff perfused hearts from albino rats. Depolarization was obtained by increasing external potassium concentration in steps (5.4, 7.4, 10, 10.5, 11 and 11.5 mM) in the perfusing solution with or without adrenaline (Adr). Left ventricle isovolumic systolic pressure and coronary flow did not change as external potassium increased, albeit being larger with Adr in the perfusing solution. Atrial and ventricular rates decreased, the latter showing a larger decline. The same behaviour was displayed by perfused hearts, with higher rates being developed by the group with Adr. PR interval and QRS complex duration increased as a function of external potassium. PR intervals were the same in both groups but QRS duration was larger in the Adr group, indicating that AV conduction was not changed in presence of Adr but intraventricular conduction was delayed in that situation. It was also observed that in the great majority of perfused hearts, differing from isolated preparations, ventricular mechanical activity ceased at around 11.5 mM external potassium.     

125~I－后标记检测DNA－蛋白质交联物的研究

１２５~Ｉ－后标记法是庄志雄等人（１９９４）提出的一种检测ＤＮＡ－蛋白质交联物（ＤＰＣｓ）的新技术，该法在检测离体ＣＨＯ细胞ＤＰＣｓ的实验中已显示出敏感、快速和简便的优点。本研究表明，１２５~Ｉ－后标记法不仅能有效地检出由紫外光和铬酸钾诱导的ＣＨＬ细胞ＤＰＣｓ，并能有效而敏感地检测由铬酸钾和氯化镍引起的大鼠不同组织特别是白细胞ＤＰＣｓ形成的情况，是一种敏感的和可考虑应用于人群调查的ＤＰＣｓ检测方法。     

内皮素-1对高血压病患者肠系膜动脉平滑肌细胞钙激活钾通道活性的影响

目的　探讨内皮素 1(ET1)对高血压病患者血管平滑肌细胞KCa通道活性的影响。方法　选择高血压病患者 18例 ,血压正常者 17例 ,两组患者均于腹部手术时取肠系膜动脉小分支用酶消化法获得单个血管平滑肌细胞。以膜片钳技术检测KCa通道的活性 ,记录不同钳制电压下单通道电流的平均开放时间 (To)、平均关闭时间 (Tc)、平均开放概率 (Po)、电流幅值 (Am) ,并绘制成电流 电压关系曲线。再分别加入Ca2 + (10 -8、10 -7、10 -6mol/L)、ET1(2× 10 9mol/L、4×10 9mol/L、6× 10 9mol/L、8× 10 9mol/L)后检测To、Tc、Po、Am等参数变化。结果　①高血压病患者KCa通道活性变化 :于细胞内面向外膜片下 ,在对称性高钾液中 ,高血压病组KCa通道平均开放概率增加 ,关闭时间延长、开放时间缩短。在浴液中分别加入Ca2 + 后 ,两组KCa通道均被明显激活 ,但血压正常组Po的增加显著高于高血压病组 (P <0 .0 0 1)。②ET1对高血压病患者KCa通道活性的影响 :血压正常者在内面向外式膜片下 ,Po、Tc均先增加后降低 ,显示低浓度时兴奋、高浓度时抑制 ,然而高血压病患者肠系膜血管平滑肌KCa通道对ET1则缺乏反应。结论　高血压病患者肠系膜动脉平滑肌细胞KCa通道活性明显高于血压正常者 ,但对Ca2 + 的敏感性降低。ET1对高血压病人KC     

ACUTE EFFECT OF ETHANOL ON RENAL ELECTROLYTE TRANSPORT IN THE RAT

1. Despite human and animal studies, the direct effect of ethanol on renal water and electrolyte transport is poorly understood. The acute effect of increasing plasma concentrations of ethanol was evaluated in a water diuretic anaesthetized rat model which inhibits endogenous arginine vaso-pressin (AVP) release. 2. Ethanol at a plasma concentration of 1.69 ±0.28 mmol/L produced an immediate increase in urine flow (174 ± 11 μL/min pre-ethanol and 189 ± 13 and then 206 ± 12 μL/min during the ethanol infusion; P<0.001) as well as an increase in fractional sodium excretion (0.17 ± 0.04 to 0.28 ± 0.05 and 0.27 ± 0.05%; P<0.001). There was also a brief phosphaturia. These increases in electrolyte excretion had returned to control values by 20 min despite a further increase in the plasma ethanol concentration. 3. The urinary excretion of potassium, calcium and magnesium was not altered nor was glomerular filtration rate or renal plasma flow. 4. Ethanol at a mean concentration of 1.60 mmol/L did not alter the action of a maximal concentration of AVP (75 ng/kg) on water or electrolyte transport. However, the antidiuretic effect of a submaximal concentration of AVP (7.5 ng/kg) was augmented by ethanol at concentrations of 1.63 and 0.98 mmol/L. 5. These studies suggest that the ethanol induced diuresis commonly ascribed to inhibition of AVP secretion may also be due to other intrarenal effects of ethanol, possibly acting within the proximal tubule. These results also confirm recent in vitro findings that while ethanol does not inhibit the action of a maximal concentration of AVP, it does modulate the effects of lower AVP concentrations.     

K~+ Channels and Their Effects on Membrane Potential in Rat Bronchial Smooth Muscle Cells

In order to investigate the K~+ channels and their effects on resting membrane potential(Em) and excitability in rat bronchial smooth muscle cells (BSMCs), the components of outward K~+channel currents and the effects of K~+ channels on Em and tension in rat bronchial smooth musclewere observed by using standard whole-cell recording of patch clamp and isometric tension recordingtechniques. The results showed that under resting conditions, total outward K~+ channel currents infreshly isolated BSMCs were unaffected by ATP-sensitive K~+ channel blocker. There were two typesof K~+ currents: voltage-dependent delayed rectifier K~+ channel (Kv) and large conductance calcium-activated K~+ channel (BK_(Ca)) currents. 1 mmol/L 4-aminopyridine (4-AP, an inhibitor of Kv)caused a significant depolarization (from — 8.7±5.9mV to —25.4±3.1mV, n=18, P<0.001).In contrast, 1 mmol/L tetraethylammonium (TEA, an inhibitor of BK_(Ca)) had no significant effect onEm (from —37.6±4.8 mV to —36.8±4.1 mV, n=12, P>0.05). 4     

心肌缺血预适应中的离子通道

缺血预适应调动机体内源性抗损伤能力，保护缺血缺氧的组织细胞，是近年来心血管领域研究的热点之一。本该对心肌缺血预适应中的离子通道、三磷酸腺苷敏感性钾通道（KATP通道）、L-型钙道道（L-Ca^2 通道）、体积调节性氯通道（Cl vol通道）的特性、作用及其机制作一综述。     

心房颤动犬心房肌细胞2型理阿诺受体的分布和表达

目的探讨心房颤动(房颤)时心房肌细胞2型理阿诺受体表达和分布的改变。方法杂种犬10只,分为正常对照组和单纯房颤组,每组5只。单纯房颤组用起搏器进行房颤式快速起搏,起搏频率(500±20)次/min,正常对照组不植入起搏器。24周后取出心脏,用逆转录聚合酶链反应、免疫荧光染色技术检测犬心房肌细胞2型理阿诺受体在mRNA水平的表达和蛋白水平的表达和分布。结果与正常对照组比较,单纯房颤组犬2型理阿诺受体在mRNA和蛋白水平的表达明显低于正常对照组(P<0.05);在细胞质、细胞膜2型理阿诺受体分布均显著减少。结论房颤时心房肌细胞2型理阿诺受体表达下调,2型理阿诺受体可能不是心房肌细胞主要的钙信号调控的受体。     

耐药性癫患者脑组织线粒体mMDHNDUFC_2基因表达异常

目的研究耐药性癫患者脑细胞线粒体mMDH、NDUFC2表达,探讨其在耐药性癫癎形成中的作用。方法分别提取48例耐药性癫癎患者、8例非耐药性癫患者及8例对照组脑组织标本的总RNA后,用基因芯片对其进行扫描,随后用荧光定量PCR技术进行验证。结果发现与线粒体功能有关的基因mMDH、NDUFC2在耐药性癫癎中显著下调,荧光定量RT—PCR验证结果与基因芯片一致。结论脑细胞线粒体基因mMDH、NDUFC2表达异常可能通过能量代谢及神经元坏死参与了耐药性癫癎的形成。