孕酮对新生鼠缺氧缺血性脑病皮层中H2O、Na+、K+、Ca2+含量的影响

目的:研究孕酮对缺氧缺血性脑病新生鼠皮层中H2+、Na+、K+、Ca2+含量的影响.方法:52只7日龄新生Wistar大鼠随机分成五组.模型组动物先行左侧颈总动脉结扎术,再吸入8%O2和92%N2的混合气体2.5 h建立缺氧缺血脑病动物模型.动物于建立模型前30 min给予不同剂量孕酮溶液,24 h取皮层组织测H2O、Na+、K+、Ca2+含量.结果:药物预防组皮层中H2O含量分别为(89.18±1.49)%、(88.57±2.44)%、(89.45±2.89)%,明显低于缺氧缺血组(91.79±2.02)%(P＜0.05),Na+、Ca2+含量亦明显低于缺氧缺血组(P＜0.05),而K+含量则明显高于缺氧缺血组.结论:孕酮可以减轻新生鼠缺氧缺血时皮层H2O、Na+、Ca2+含量,升高K+含量,从而减轻脑水肿.     

孕酮对新生鼠缺氧缺血性脑病皮层中H20、Na＋、K＋、Ca^2＋含量的影响

目的:研究孕酮对缺氧缺血性脑病新生鼠皮层中H2+、Na+、K+、Ca2+含量的影响.方法:52只7日龄新生Wistar大鼠随机分成五组.模型组动物先行左侧颈总动脉结扎术,再吸入8%O2和92%N2的混合气体2.5 h建立缺氧缺血脑病动物模型.动物于建立模型前30 min给予不同剂量孕酮溶液,24 h取皮层组织测H2O、Na+、K+、Ca2+含量.结果:药物预防组皮层中H2O含量分别为(89.18±1.49)%、(88.57±2.44)%、(89.45±2.89)%,明显低于缺氧缺血组(91.79±2.02)%(P＜0.05),Na+、Ca2+含量亦明显低于缺氧缺血组(P＜0.05),而K+含量则明显高于缺氧缺血组.结论:孕酮可以减轻新生鼠缺氧缺血时皮层H2O、Na+、Ca2+含量,升高K+含量,从而减轻脑水肿.     

PI3K/Akt/FoxO3a/Bim信号通路介导硫化氢后处理对缺氧H9c2心肌细胞的保护作用

目的探讨硫氢化钠(Na HS)后处理是否通过PI3K/Akt/Fox O3a/Bim信号通路调节细胞凋亡发挥减轻心肌细胞缺氧/复氧(H/R)损伤的作用。方法 H9c2大鼠心肌细胞缺氧3 h/复氧6 h,建立缺氧/复氧损伤模型。将细胞随机分为5组:空白组(Control组)、缺氧/复氧组(H/R组)、硫氢化钠后处理组(H/R+Na HS组)、抑制剂LY294002组(H/R+LY组)、硫氢化钠后处理+LY294002组(H/R+Na HS+LY组)。分别在缺氧前、复氧末检测H9c2心肌细胞的存活率以及LDH释放;流式细胞术检测各组的细胞凋亡率;应用Western blot检测Akt、p-Akt、Fox O3a、p-Fox O3a、Bim蛋白的表达水平;免疫荧光检测Fox O3a的分布情况。结果缺氧前各组心肌细胞存活率、LDH释放量差异无统计学意义(P>0.05)。复氧末,Na HS组与H/R组相比,心肌细胞存活率明显提高(P<0.05),LDH释放量与细胞凋亡率明显降低(P<0.05);p-Akt、p-Fox O3a蛋白表达水平升高,Bim表达降低,同时Fox O3a在细胞质的表达升高。LY294002逆转了Na HS后处理产生的心肌细胞保护作用,使得H/R+Na HS+LY组的心肌细胞存活率降低(P<0.05)、LDH释放和细胞凋亡率升高(P<0.05),p-Akt、p-Fox O3a蛋白表达降低(P<0.05),Bim表达升高(P<0.05),FoxO 3a在细胞质的表达水平降低。结论硫氢化钠(NaH S)后处理通过PI3K/Akt/FoxO 3a/Bim信号通路调控细胞凋亡,减轻心肌细胞缺氧/复氧(H/R)损伤。     

广枣总黄酮对大鼠心室肌细胞IC_a、I_(to)和细胞[Ca~(2+)]_i的影响

目的　观察广枣总黄酮对大鼠心室肌细胞L 型钙通道电流 (ICa)和瞬时外向钾通道电流 (Ito)以及对心肌细胞内游离钙浓度 ([Ca2 + ]i)的影响 ,探讨其抗心律失常作用机制。方法　全细胞膜片钳记录大鼠心室肌细胞ICa、Ito,激光共聚焦显微镜观察细胞 [Ca2 + ]i 的变化。结果　在钳制电压- 4 0mV ,实验电压 - 4 0～ +5 0mV时 ,广枣总黄酮 10 0mg·L-1对心室肌细胞ICa无显著影响 ;在钳制电压 - 6 0mV ,实验电压 - 4 0～ +5 0mV时显著抑制瞬时外向钾通道Ito(P <0 0 5 ) ;而激光共聚焦显微镜结果显示广枣总黄酮在 5 0、10 0、2 0 0mg·L-1却降低缺氧复氧心肌细胞收缩期和静息期[Ca2 + ]i 的浓度。结论　广枣总黄酮对心肌细胞ICa无显著影响 ,可显著抑制瞬时外向钾通道Ito,并可明显降低心肌细胞收缩期和静息期细胞 [Ca2 + ]i 浓度。这可能是其抗心律失常和保护缺血心肌的主要作用机制。     

阿米洛利对大鼠压力超负荷性心肌肥厚的抑制作用

目的　观察钠氢交换体 (NHE)抑制剂阿米洛利 (Ami)对压力超负荷左室肥厚 (LVH)大鼠心功能、心肌细胞内游离钙浓度 ([Ca2 + ]i)及心肌细胞膜Na+ 、K+ ATP酶活性的影响。方法　①同步记录离体工作心脏LVSP、LVEDP、±dp/dtmax及T值 ;②测定Fura 2 /A负载后的单个心室肌细胞的 [Ca2 + ]i;③光电比色法测定Na+ 、K+ ATP酶的活性。结果　①与对照组相比 ,LVH组LVEDP和T值明显增加 ,-dp/dtmax明显降低 (均P <0 0 1) ;与LVH组相比 ,Ami组和Ena组的LVEDP及T值明显下降 (均P <0 0 1)。②与对照组相比 ,LVH组的心肌细胞 [Ca2 + ]i明显增高 ,细胞膜Na+ 、K+ ATP酶活性明显降低 (均P <0 0 1) ;Ami及Ena可降低LVH大鼠的 [Ca2 + ]i,升高其Na+ 、K+ ATP酶活性 (均P <0 0 1)。结论　压力超负荷大鼠心脏舒张功能明显下降 ,心室肌细胞 [Ca2 + ]i增高 ,心肌细胞膜Na+ 、K+ ATP酶活性受损 ,Ami及Ena均可抑制此类异常     

牛磺酸对染铅大鼠心肌脂质过氧化及心肌细胞膜ATP酶活力的影响

目的观察牛磺酸对染铅大鼠心肌细胞膜ATP酶活性及心肌脂质过氧化损伤的影响。方法用醋酸铅溶液灌胃制备大鼠染铅模型,实验完后断颈处死大鼠测定心肌铅含量及超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)和谷胱甘肽过氧化物酶(GSH-Px)水平。并取心肌细胞测定心肌细胞膜Na+-K+、Ca2+-Mg2+ATP酶活性。结果 牛磺酸各剂量组[200、400和800 mg/(kg.d)]连续灌胃给药后,对心肌细胞膜Na+-K+、Ca2+-Mg2+ATP酶活性均有不同的升高作用(P0.05或P0.01)。而对铅所致大鼠心肌过氧化损伤均有不同的降低作用(P0.05或P0.01)。结论牛磺酸对铅所致大鼠心肌细胞膜ATP酶活性降低及心肌细胞过氧化损伤具有明显的保护作用。     

氯胺酮抗惊厥的作用机制

目的观察氯胺酮对惊厥小鼠不同脑区Na+,K+-ATP酶、Ca2+-ATP酶以及NOS酶活性的影响,探讨氯胺酮抗惊厥作用的中枢机制。方法昆明种小鼠随机分成空白组、生理盐水(NS)组、氯胺酮25mg·kg-1(KetⅠ)和50mg·kg-1(KetⅡ)组。空白组直接断头取脑。其余各组分别ip相应药物,5min后ip士的宁1.5mg·kg-1诱发惊厥,观察惊厥小鼠行为学变化,并于给士的宁30min后断头,用分光光度计法测定皮层额、顶、枕脑区的Na+,K+-ATP酶、Ca2+-ATP酶和NOS酶活性。结果氯胺酮组明显降低动物死亡率,KetⅡ组惊厥持续期较KetⅠ组明显缩短。与空白组相比,NS组和KetⅠ组Na+,K+-ATP酶、Ca2+-ATP酶活性均有降低,KetⅡ组顶、枕区Na+,K+-ATP和Ca2+-ATP酶活性维持在正常水平;KetⅡ组TNOS酶活性降低约1/3(P<0.05),各组对iNOS活性均无影响。结论氯胺酮抗惊厥作用机制可能与增加大脑皮层顶枕区的Na+,K+-ATP和Ca2+-ATP酶活性、降低cNOS酶活性有关。     

穿心草口山酮对激活细胞膜Na~+/H~+交换加重心脏缺血再灌注损伤的保护作用

目的　研究 3种穿心草口山酮 (xanthone ,Xan) :1,8 dihydroxy ,3 ,5 dimethoxyxanthone(Xan Ⅰ ) ;1 hydroxy ,3 ,5 dimethoxyxanthone(Xan Ⅱ ) ;1 hydroxy ,3 ,7,8 trithoxyxan thone(Xan Ⅲ )对激活细胞膜Na+/H+交换加重心脏缺血再灌注损伤的保护作用。方法　在离体大鼠等容收缩模型上 ,采用NH4 Cl负荷方法以激活细胞膜Na+/H+交换 ,观察在缺血前给予Xan对缺血再灌注损伤的影响。结果　Na+/H+交换组增加冠脉流出液中乳酸脱氢酶 (LDH)的含量 ,促进心肌组织脂质过氧化产物丙二醛 (MDA)的生成 ,加重心肌组织中Na+、Ca2 +超负荷和K+的丢失。浓度为 0 2 μmol·L-1的Xan可明显减轻上述作用 ,作用强度依次为Xan Ⅰ>Xan Ⅲ >Xan Ⅱ。结论　穿心草 3种Xan对激活细胞膜Na+/H+交换加重心脏缺血再灌注损伤有一定的保护作用。     

玉郎伞两种黄酮单体对心肌细胞缺氧/复氧损伤的保护作用

目的研究从玉郎伞(Yulangsan,YLS)中首次分离的两种黄酮单体对体外培养大鼠乳鼠心肌细胞缺氧/复氧损伤的保护作用,并初步探讨其作用机制。方法建立体外培养大鼠乳鼠心肌细胞缺氧/复氧损伤模型,倒置显微镜下观察加入YLS两种单体的含药血清(10%、5%、2.5%)后,各组缺氧/复氧心肌细胞形态学和搏动频率的变化;以MTT法检测各组细胞的存活率;用ELISA法测定心肌细胞Na+,K+-ATP酶、Ca2+,Mg2+-ATP酶活性及细胞培养上清液中总超氧化物歧化酶(T-SOD)、乳酸脱氢酶(LDH)、一氧化氮合酶(NOS)活性和丙二醛(MDA)含量。结果与模型组相比,YLS两种单体含药血清的高、中剂量均能明显增加心肌细胞的存活率,增强Na+,K+-ATP酶、Ca2+,Mg2+-ATP酶活性,降低细胞培养上清液LDH、NOS活性、MDA含量,提高T-SOD活性并呈剂量依赖性(P<0.05)。结论两种YLS单体对体外培养大鼠乳鼠心肌细胞缺氧/复氧损伤具有保护作用,其机制可能与清除自由基、抑制心肌细胞Ca2+超载有关。     

MitoKATP通道开放对重症急性胰腺炎大鼠心肌的保护作用

目的:探讨线粒体ATP敏感性钾(MitoKATP)通道开放对重症急性胰腺炎(SAP)心肌的保护作用及机制.方法:清洁级雄性SD大鼠36只随机分为4组,K组假手术;M组建立SAP大鼠模型;D组和H组分别给予连续腹腔注射二氮嗪(DZ)、DZ+5-羟基葵酸盐(5-HD)3 d后建立SAP大鼠模型.检测4组大鼠术后24h血清肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)水平;分光光度法测定心肌组织Na+-K+-ATPase活性;流式细胞仪检测心肌细胞线粒体膜电位(△ψm)变化;原位末端标记(TUNEL)法检测心肌细胞凋亡情况;留取部分心脏、胰腺组织行病理学检查.结果:M组CK-MB、LDH水平、心脏病理评分及凋亡指数较D组升高,Na+-K+-ATPase活性及△ψm较D组降低,差异均有统计学意义(P＜0.01),但M组上述指标与H组比较差异均无统计学意义(P＞0.05).结论:MitoKATP通道开放对SAP引起的心肌损伤有保护作用,且上述作用可被该通道阻滞剂阻断.     

Reciprocal effects of glucose on the process of cell death induced by calcium ionophore or H2O2 in rat lymphocytes

We have examined the effects of glucose at high concentrations on the process of cell death induced by excessive increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) or oxidative stress in rat lymphocytes. The cell death elicited by the excessive increase in [Ca(2+)](i) seemed to be induced by an activation of Ca(2+)-dependent K(+) channels because the inhibitors for Ca(2+)-dependent K(+) channels attenuated the decrease in cell viability. Glucose at 30-50mM augmented the decrease in cell viability by the excessive increase in [Ca(2+)](i). It was not specific for glucose because it was the case for sucrose or NaCl, suggesting an involvement of increased osmolarity in adverse action of glucose. On the contrary, glucose protected the cells suffering from oxidative stress induced by H(2)O(2), one of reactive oxygen species. It was also the case for fructose or sucrose, but not for NaCl. The process of cell death induced by H(2)O(2) started, being independent from the presence of glucose. Glucose delayed the process of cell death induced by H(2)O(2). Sucrose and fructose also protected the cells against oxidative stress. The reactivity of sucrose to reactive oxygen species is lower than those of glucose and fructose. The order in the reactivity cannot explain the protective action of glucose. Glucose at high concentrations exerts reciprocal actions on the process of cell death induced by the oxidative stress and excessive increase in [Ca(2+)](i).     

The gasotransmitter hydrogen sulphide decreases Na⁺ transport across pulmonary epithelial cells

BACKGROUND AND PURPOSE The transepithelial absorption of Na(+) in the lungs is crucial for the maintenance of the volume and composition of epithelial lining fluid. The regulation of Na(+) transport is essential, because hypo- or hyperabsorption of Na(+) is associated with lung diseases such as pulmonary oedema or cystic fibrosis. This study investigated the effects of the gaseous signalling molecule hydrogen sulphide (H(2) S) on Na(+) absorption across pulmonary epithelial cells. EXPERIMENTAL APPROACH Ion transport processes were electrophysiologically assessed in Ussing chambers on H441 cells grown on permeable supports at air/liquid interface and on native tracheal preparations of pigs and mice. The effects of H(2)S were further investigated on Na(+) channels expressed in Xenopus oocytes and Na(+) /K(+)-ATPase activity in vitro. Membrane abundance of Na(+) /K(+)-ATPase was determined by surface biotinylation and Western blot. Cellular ATP concentrations were measured colorimetrically, and cytosolic Ca(2+) concentrations were measured with Fura-2. KEY RESULTS H(2)S rapidly and reversibly inhibited Na(+) transport in all the models employed. H(2)S had no effect on Na(+) channels, whereas it decreased Na(+) /K(+)-ATPase currents. H(2)S did not affect the membrane abundance of Na(+) /K(+)-ATPase, its metabolic or calcium-dependent regulation, or its direct activity. However, H(2)S inhibited basolateral calcium-dependent K(+) channels, which consequently decreased Na(+) absorption by H441 monolayers. CONCLUSIONS AND IMPLICATIONS H(2) S impairs pulmonary transepithelial Na(+) absorption, mainly by inhibiting basolateral Ca(2+)-dependent K(+) channels. These data suggest that the H(2)S signalling system might represent a novel pharmacological target for modifying pulmonary transepithelial Na(+) transport.     

High affinity interaction of mibefradil with voltage-gated calcium and sodium channels

Mibefradil is a novel Ca(2+) antagonist which blocks both high-voltage activated and low voltage-activated Ca(2+) channels. Although L-type Ca(2+) channel block was demonstrated in functional experiments its molecular interaction with the channel has not yet been studied. We therefore investigated the binding of [(3)H]-mibefradil and a series of mibefradil analogues to L-type Ca(2+) channels in different tissues. [(3)H]-Mibefradil labelled a single class of high affinity sites on skeletal muscle L-type Ca(2+) channels (K(D) of 2.5+/-0.4 nM, B(max)=56.4+/-2.3 pmol mg(-1) of protein). Mibefradil (and a series of analogues) partially inhibited (+)-[(3)H]-isradipine binding to skeletal muscle membranes but stimulated binding to brain L-type Ca(2+) channels and alpha1C-subunits expressed in tsA201 cells indicating a tissue-specific, non-competitive interaction between the dihydropyridine and mibefradil binding domain. [(3)H]-Mibefradil also labelled a heterogenous population of high affinity sites in rabbit brain which was inhibited by a series of nonspecific Ca(2+) and Na(+)-channel blockers. Mibefradil and its analogue RO40-6040 had high affinity for neuronal voltage-gated Na(+)-channels as confirmed in binding (apparent K(i) values of 17 and 1.0 nM, respectively) and functional experiments (40% use-dependent inhibition of Na(+)-channel current by 1 microM mibefradil in GH3 cells). Our data demonstrate that mibefradil binds to voltage-gated L-type Ca(2+) channels with very high affinity and is also a potent blocker of voltage-gated neuronal Na(+)-channels. More lipophilic mibefradil analogues may possess neuroprotective properties like other nonselective Ca(2+)-/Na(+)-channel blockers.     

Heterogeneous increases of cytoplasmic calcium: distinct effects on down-regulation of cell surface sodium channels and sodium channel subunit mRNA levels

1. Long-term (> or = 12 h) treatment of cultured bovine adrenal chromaffin cells with A23187 (a Ca(2+) ionophore) or thapsigargin (TG) [an inhibitor of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)] caused a time- and concentration-dependent reduction of cell surface [(3)H]-saxitoxin (STX) binding capacity, but did not change the K:(D:) value. In A23187- or TG-treated cells, veratridine-induced (22)Na(+) influx was reduced (with no change in veratridine EC(50) value) while it was enhanced by alpha-scorpion venom, beta-scorpion venom, or Ptychodiscus brevis toxin-3, like in nontreated cells. 2. The A23187- or TG-induced decrease of [(3)H]-STX binding was diminished by BAPTA-AM. EGTA also inhibited the decreasing effect of A23187. A23187 caused a rapid, monophasic and persistent increase in intracellular concentration of Ca(2+) ([Ca(2+)](i)) to a greater extent than that observed with TG. 2,5-Di-(t-butyl)-1,4-benzohydroquinone (DBHQ) (an inhibitor of SERCA) produced only a rapid monophasic increase in [Ca(2+)](i), without any effect on [(3)H]-STX binding. 3. Reduction in [(3)H]-STX binding capacity induced by A23187 or TG was attenuated by G?6976 (an inhibitor of conventional protein kinase C) or calpastatin peptide (an inhibitor of calpain). When the internalization rate of cell surface Na(+) channels was measured in the presence of brefeldin A (an inhibitor of vesicular exit from the trans-Golgi network), A23187 or TG accelerated the reduction of [(3)H]-STX binding capacity. 4. Six hours treatment with A23187 lowered Na(+) channel alpha- and beta(1)-subunit mRNA levels, whereas TG had no effect. 5. These results suggest that elevation of [Ca(2+)](i) caused by A23187, TG or DBHQ exerted differential effects on down-regulation of cell surface functional Na(+) channels and Na(+) channel subunit mRNA levels.     

Riluzole inhibits spontaneous Ca2+ signaling in neuroendocrine cells by activation of K+ channels and inhibition of Na+ channels

The neuroprotective drug riluzole has multiple effects on cellular signaling. We found that riluzole rapidly and reversibly inhibited spontaneous Ca2+ oscillations in both immortalized GnRH-secreting hypothalamic neurons (GT1 cells) and in the prolactin and growth-hormone-secreting GH3 cell line. At lower concentrations (100 nm-5 microM), riluzole reduced the amplitude and frequency of spontaneous Ca2+ oscillations, whereas at higher concentrations it abolished spontaneous Ca2+ signaling. Whole-cell current clamp recordings in GH3 cells revealed that riluzole decreased the action potential frequency, amplitude, and duration. Riluzole inhibited voltage-gated Na+ currents, increased iberiotoxin-sensitive voltage-gated K+ currents, and had no effect on voltage-gated Ca2+ currents in GH3 cells. Riluzole also inhibited voltage-gated Na+ currents and increased voltage-gated K+ channels in GT1 cells. The inhibitory effects of riluzole on Ca2+ signaling were blocked by pretreatment with iberiotoxin in GH3 cells, but only partially reduced by iberiotoxin in GT1 cells. These results indicate that riluzole inhibits Ca2+ signaling primarily by activation of K+ channels in GH3 cells, and also by inhibition of Na+ channels in GT1 cells. Riluzole's inhibition of spontaneous excitability and Ca2+ signaling may be involved in its multiple effects on cellular function in the nervous system.     

TRPM2

TRPM2 is a cation channel enabling influx of Na+ and Ca2+, leading to depolarization and increases in the cytosolic Ca2+ concentration ([Ca2+]i). It is widely expressed, e.g. in many neurons, blood cells and the endocrine pancreas. Channel gating is induced by ADP-ribose (ADPR) that binds to a Nudix box motif in the cytosolic C-terminus of the channel. Endogenous ADPR concentrations in leucocytes are sufficiently high to activate TRPM2 in the presence of an increased [Ca2+]i but probably not at resting [Ca2+]i. Another channel activator is oxidative stress, especially hydrogen peroxide (H2O2) that may act through ADPR after ADPR polymers have been formed by poly(ADP-ribose) polymerases (PARPs) and hydolysed by glycohydrolases. H2O2-stimulated TRPM2 channels essentially contribute to insulin secretion in pancreatic beta-cells and alloxan-induced diabetes mellitus. Inhibition of TRPM2 channels may be achieved by channel blockers such as flufenamic acid or the anti-fungal agents clotrimazole or econazole. Selective blockers of TRPM2 are not yet available; those would be valuable for a characterization of biological roles of TRPM2 in various tissues and as potential drugs directed against oxidative cell damage, reperfusion injury or leucocyte activation. Activation of TRPM2 may be prevented by anti-oxidants, PARP inhibitors and glycohydrolase inhibitors. In future, binding of ADPR to the Nudix box may be targeted. In light of the wide-spread expression and growing list of cellular functions of TRPM2, useful therapeutic applications are expected for future drugs that block TRPM2 channels or inhibit their activation.     

绞股蓝总皂苷对光化学诱导大鼠大脑中动脉栓塞性脑缺血损伤的保护作用

目的研究绞股蓝总皂苷(Gyp)对栓塞性脑缺血损伤的保护作用。方法应用光化学诱导大鼠大脑中动脉栓塞模型,观察Gyp预防性给药后脑组织超氧化物歧化酶(SOD)活力,脂质过氧化产物TBARS,钠、钾、钙和水的含量以及缺血区范围的变化。结果Gyp能缩小光化学反应后的缺血区面积,降低TBARS含量,提高SOD活性,降低缺血区Na     

Osteoclast ion channels: potential targets for antiresorptive drugs

This review summarizes the types of ion channels that have been identified in osteoclasts and considers their potential as targets for therapeutic agents aimed at the treatment of osteoporosis and other bone disorders. We focus on channels that have been identified using molecular and electrophysiological approaches. Numerous ion channels have been characterized, including K(+), H(+), Na(+), nonselective cation and Cl(-) channels. K(+) channels include an inward rectifier K(+) channel (Kir2.1) that is regulated by G proteins, and a transient outward rectifier K(+) channel (Kv1.3) that is regulated by cell-matrix interactions and by extracellular cations such as Ca(2+) and H(+). In addition, two classes of Ca(2+)-activated K(+) channels have been described--large and intermediate conductance channels, which are activated by increases of cytosolic Ca(2+) concentration. Other channels include stretch-activated nonselective cation channels and voltage-activated H(+) channels. A recent revelation is the presence of ligand-gated channels in osteoclasts, including P2X nucleotide receptors and glutamate-activated channels. Osteoclasts also exhibit an outwardly rectifying Cl(-) current that is activated by cell swelling. Kir2.1 and Cl(-) channels may be essential for resorptive activity because they provide pathways to compensate for charge accumulation arising from the electrogenic transport of H(+). As in other cell types, osteoclast ion channels also play important roles in setting the membrane potential, signal transduction and cell volume regulation. These channels represent potential targets for the development of antiresorptive drugs.     

多塞平对大鼠急性脑缺血再灌注损伤的保护作用

目的：观察多塞平对大鼠急性脑缺血再灌注引起损伤的保护作用。方法：６０只大鼠，分为多塞平大、中、小剂量（１５，１０，５ｍｇ／ｋｇ）组，尼莫地平阳性对照组、空白对照组和假手术对照组。用阻断四血管方法造成大鼠急性脑缺血再灌注损伤，原子吸收分光光度计测定脑组织Ｃａ２＋，Ｎａ＋，Ｋ＋的含量。结果：与空白对照组比较，尼莫地平阳性对照组和多塞平大、中剂量组脑组织Ｃａ２＋，Ｎａ＋，Ｈ２Ｏ含量显著降低（Ｐ＜０．０５或Ｐ＜０．０１）；多塞平小剂量组脑组织Ｃａ２＋含量显著降低（Ｐ＜０．０５），其余含量变化均不显著（Ｐ＞０．０５）。结论：多塞平能显著降低因缺血引起的脑组织Ｃａ２＋，Ｎａ＋，Ｈ２Ｏ含量增高，表现出钙拮抗作用     

Potassium and potassium clouds in endothelium-dependent hyperpolarizations

A small increase in extracellular K(+) acts as a local, physiological regulator of blood flow to certain vascular beds. The K(+) derives from active tissues such as contracting skeletal muscle and brain and increases blood supply to these organs by the activation of Na(+)/K(+)-ATPases and/or inwardly-rectifying K(+) channels on the vascular myocytes. K(+) liberated from the vascular endothelium also acts as an endothelium-derived hyperpolarizing and relaxing factor within blood vessels. The K(+) effluxes from endothelial cell intermediate- and small-conductance, Ca(2+)-sensitive K(+) channels which open in response to stretch and local hormones. In many vessels, endothelium-derived hyperpolarizing factor (EDHF) seems identical to the K(+) derived from endothelial cells; it activates Na(+)/K(+)-ATPases (particularly those containing alpha2 and alpha3 subunits) and inward rectifiers (particularly Kir2.1) located on the vascular myocytes. Vasospastic agents generate "potassium clouds" around vascular smooth muscle cells via the efflux of this ion through large conductance, Ca(2+)-sensitive K(+) channels on the myocytes. These potassium clouds can reduce the hyperpolarizing actions of endothelium-derived K(+) by effectively saturating the Na(+)/K(+)-ATPases and inward rectifiers on the muscle cells and they may be of clinical significance in vasospastic conditions.