阿霉素中毒心肌细胞钙离子调节功能的变化

本文采用Fura-2/AM荧光标记同位素~(45)Ca~(2+)负载示踪法测定了心肌细胞内钙浓度及肌浆网摄钙功能,探讨了阿霉素对心肌细胞内钙调节功能的影响,同时还观察了维拉帕米预处理10min后,阿霉素对心肌细胞内钙浓度及钙调节功能的影响.结果显示,阿霉素作用早期(10min)能够增加心肌细胞外钙的快相内流,使心肌细胞内游离钙浓度增高,肌浆网摄钙量也有轻度增加,阿霉素作用60min后,与对照组相比细胞内~(45)Ca~(2+)总量增加,而肌浆网对~(45)Ca~(2+)的摄取明显减低,细胞浆内游离钙浓度明显升高.维拉帕米预处理组,维拉帕米部分阻断了阿霉素对细胞内钙的调节作用.结果提示,阿霉素通过增加心肌细胞钙内流速度和抑制肌浆网摄钙量,导致心肌细胞钙过负荷,进而影响心肌细胞的收缩舒张功能.     

锰对心室肌电机械活动及窦房结细胞电活动的影响

本实验观察了不同浓度的 Mn~(2+)对豚鼠心肌细胞电机械活动、Ba~(2+)所诱发的心室肌自发电活动以及窦房结电活动的影响。结果表明:低浓度(0.05—0.5mM)的 Mn~(2+)使心肌细胞 APD_(50)、APD_(90)、ERP 延长,但 ERP/APD 比值减小。低浓度的 Mn~(2+)对心肌收缩力抑制不明显,而高浓度的 Mn~(2+)对心肌收缩力有较强的抑制作用。2—4mM 的 Mn~(2+)能使 Ba~(2+)所诱发的心室肌自发电活动消失。0.5mM 的 Mn~(2+)使窦房结细胞 APA、Vmax、SP_4减小,窦搏率减慢.2mM 以上的 Mn~(2+)可使其 AP 消失。提示:Mn~(2+)可抑制心脏自发电活动。     

铬灌流对大鼠心肌细胞电生理影响

本研究采用灌流方法观察铬对大鼠心肌细胞的电生理效应。结果表明:铬可使心肌细胞的APD缩短,而对AP的其它参数无作用。用1.9×10~(-5)mol/L灌流时,APD_(50)和APD_(90)均缩短,5min时开始缩短,20～30min时达最大值,60min时由缩短又开始延长;1.9×10~(-6)mol/L时,APD也缩短,但幅度较小;9.6×10~(-5)mol/L时、APD虽明显缩短,但心肌的应激性明显降低。心肌细胞APD的缩短,可能是铬影响了钙离子及钾离子流的结果。     

镁对离体大鼠正常和缺血心脏室颤阈值的影响

本文观察Mg~(2 )对正常和局部缺血离体大鼠心脏VFT的影响。结果表明:提高灌流液Mg~(2 )浓度(正常值2倍)时,可使正常或局部缺血大鼠心脏的VFT增高;提高灌流液Ca~(2 )(正常值2倍)时,VFT下降,若再提高Mg~(2 )浓度,可使已下降的VFT增高;高Mg~(2 )使正常和高Ca(2 )时心室的收缩强度减弱。提示高Mg(2 )降低心室易颤性的机理可能是通过竞争拮抗减少Ca~(2 )内流,降低细胞内Ca~(2 )含量有关。     

辅酶Q10对异丙基肾上腺素心肌损伤电活动的保护作用

本实验在大鼠右心室乳头肌上观察辅酶 Q_(10)在预防异丙基肾上腺素(异丙肾)所致心肌损伤细胞电活动的影响。异丙肾可影响心肌细胞去极化和复极化过程,使 APA、OS 和 RP 降低、APD 延长、Vmax 下降;辅酶 Q_(10)可减轻异丙肾对心肌细胞的电效应,使 APD 缩短、特别是 APD_(50)的缩短尤为明显。实验结果表明:辅酶 Q_(10)对心肌的保护作用,可能与阻滞细胞膜慢通道、减少细胞内钙负荷有关。     

Ca~(2+)与肝细胞增殖

本文综述了Ca~(2+)作为第二信使在肝细胞增殖中的信息传递作用。细胞内Ca~(2+)([Ca~(2+)]i)浓度升高是通过生长因子和癌蛋白等与细胞膜的相应受体结合,启动磷酯酰肌醇系统,进一步作用于细胞内钙库使其释放,或通过激活细胞膜Ca~(2+)通道使Ca~(2+)内流增加。[Ca~(2+)]i升高后,激活一些酶,使底物蛋白磷酸化,最后将信息传到核内,促进DNA复制使细胞增殖分裂。本文并对Ca~(2+)与肝再生、肝纤维化和肝癌的发生、发展的关系进行介绍。     

钙调素拮抗剂——三氟拉嗪对急性冠状动脉闭塞及再通后的心肌的保护作用

急性心肌梗塞的治疗效果有赖于再灌注期间缺血心肌功能的恢复。再灌注能加重缺血心肌的损伤。再灌注过程中,心肌细胞内Ca~(2+)积蓄将引起多种细胞内改变最终导致不可逆损伤。以往的研究表明,Ca~(2+)慢通道阻滞剂未能阻止再灌注时细胞内 Ca~(2+)积蓄,大量的 Ca~(2+)进入心肌细胞并非通过 Ca~(2+)慢     

钙库操纵性钙通道在介导低氧诱导性肺动脉高压形成中的作用及影响因素

钙库操纵性钙通道对于维持细胞内Ca~(2+)稳态起着关键作用,特别在低氧诱导性肺动脉高压的形成过程中,钙库操纵性钙通道的组成成分表达增加导致肺动脉平滑肌细胞内Ca~(2+)稳态失调,引起肺动脉平滑肌细胞过度增生、迁移,最终形成肺动脉高压。Ca~(2+)是细胞内重要的第二信使,许多信号通路的共同终末途径都聚焦于钙库操纵性钙通道介导的Ca~(2+)内流。因此,研究钙库操纵性钙通道的组成成分和功能对于低氧诱导性肺动脉高压的治疗极其关键。现就目前钙库操纵性钙通道的组成成分及其影响因素做一综述,以期寻求新的治疗靶点。     

肌质网基因表达异常——可能是衰竭心肌缩舒特性改变的机制之一

心肌收缩和舒张是由细胞内Ca~(2+)浓度调节。而后者主要是通过肌质网(SR)对Ca~(2+)的释放和摄取所控制。通过SR钙释放通道即ryranodine受体(RYR)释放Ca~(2+),触发心肌收缩。RYR有二种异构体,心肌中只有RYR2异构体。而心肌舒张则由SRCa~(2+)ATP酶摄取Ca~(2+)而起动。Ca~(2+)ATP酶有五种异     

刺激兔下丘脑背内侧核对在位心肌跨膜电位、阳离子和代谢的影响

给麻醉兔电刺激下丘脑背内侧核(DMH)可使心肌静息电位、动作电位幅度、Vmax明显下降,APD_(80)明显缩短,ST段显著抬高。给酚妥拉明后,DMH刺激不再引起上述变化。DMH刺激还引起心肌K~ /Na~ 与Mg~(2 )/Ca~(2 )下降,ATP减少和乳酸浓度增加。实验结果提示DMH刺激所诱发的心肌电变化可能与冠脉α-受体兴奋性收缩引起的心肌缺血有关。     

脑血管疾病病人脑脊液中NO和GSH-Px及锌离子的水平研究

目的探讨一氧化氮（NO）、谷胱甘肽过氧化物酶（GSH-Px）和锌离子在不同脑血管疾病病人脑脊液中的变化和意义.方法分别检测不同程度及不同渗透压脑出血、蛛网膜下腔出血病人脑脊液（CSF）中NO、GSH-Px和锌离子的水平,并分析其临床意义.结果在各种脑血管疾病病人中的重症组NO均明显高于轻症组（P〈0.05）,而轻症组又明显高于对照组（P〈0.05）;GSH-Px、锌离子明显低于轻症组,而轻症组又明显低于对照组.CSF中NO和GSH-Px呈负相关（r=-0.57,P〈0.05）,锌离子与GSH-Px呈正相关（r=0.68,P〈0.05）.CSF渗透压高组的NO含量显著高于渗透压低组（P〈0.05）,而CSF渗透压高组的GSH-Px含量显著低于渗透压低组.结论检测CSF中 NO、GSH-Px及锌离子含量可推断脑出血及蛛网膜下腔出血病人被自由基损伤的程度和清除自由基的水平.     

Calmodulin and CaMKII as molecular switches for cardiac ion channels

Because changes in intracellular Ca(2+) concentration are the final signals of electrical activity in excitable cells, many mechanisms have evolved to regulate Ca(2+) influx. Among the most important are those pathways that directly regulate the ion channels responsible for regulating and generating the Ca(2+) influx signal. Recent work has demonstrated that the Ca(2+) binding protein calmodulin (CaM) and the Ca(2+)/CaM-sensitive kinase CaMKII are important modulators of cardiac ion channels. Thus, Ca(2+) participates in feedback modulation to control electrical activity. This review highlights various mechanisms by which CaM and CaMKII regulate cardiovascular ion channel activity and presents a novel model for CaMKII regulation of Ca(V)1.2 Ca(2+) channel function.     

基质对日本血吸虫培养细胞SDH和LDH影响的研究

目的　研究细胞外基质 (ECM)对日本血吸虫培养细胞琥珀酸脱氢酶 (SDH)和乳酸脱氢酶 (L DH)代谢活力的影响 ,筛选适合培养细胞存活、生长的生物基质。　方法　将虫龄 2 1d的日本血吸虫细胞接种于预先涂有肝、肺、鼠尾胶等不同生物基质的小盖玻片上常规培养 ,运用酶细胞化学方法 ,在培养第 3d进行 SDH染色 ,第 7d作 L DH染色 ,显微镜观察并拍照 ,图像分析仪测定其含量 ,并作统计分析。　结果　不同 ECM培养的细胞 ,其 SDH、 L DH活性不同 ,着色颗粒颜色按对照组、鼠尾胶组、肺基质组、肝基质组依次加深。定量分析结果显示 ,肝、肺基质组培养细胞 SDH含量与对照组差异显著 (P<0 .0 1) ,而鼠尾胶组与对照组差异不显著 (P>0 .0 5 )。各基质组培养细胞的 L DH含量与对照组比较 ,差异显著 (P<0 .0 1) ;各基质组之间两两比较差异亦具有显著性。肝基质组培养细胞内两种酶含量最高。　结论　肝基质最适合日本血吸虫培养细胞的存活与生长。     

Effect of magnesium on neural activities in vitro

It has been well known that magnesium ion (Mg(2+)) plays an important role in biological functions, especially in neural activities and functions. However, not so many researches have been carried to this subject. Here we investigated the Mg(2+)effect on neuronal electrical activities together with NMDA receptor and synaptic glutamate release by using Multi-Electrode Array (MEA) and Enzyme modified MEA-based multi-array sensor.     

Synchronized rhythms in chemosensitive neurons of the locus coeruleus in the absence of chemical synaptic transmission.

The activity of locus coeruleus (LC) neurons was examined in the en bloc isolated brainstem-spinal cord of the neonatal rat using paired whole cell or whole cell plus extracellular recording. In artificial cerebrospinal fluid (ACSF) LC neurons were synchronized by their respiratory innervation and in some neurons showing tonic or burst patterns of discharge these patterns of discharge could also be synchronized. Replacing ACSF with low Ca(2+)-high Mg(2+) generated synchronized rhythmic bursts which remained synchronized at high CO(2) (up to 20%). This rhythm was suppressed by TTX. Substitution of Ba(2+) for Ca(2+) in ACSF generated a synchronized rhythm which was TTX-insensitive. The frequency of this rhythm increased by 31+/-16% on raising CO(2) concentration from 2 to 10%. We conclude that the capacity of chemosensitive LC neurons to generate a synchronized rhythm depends on their electrical coupling, but not on chemical synaptic transmission.     

Influence of interleukin-2 on Ca2+ handling in rat ventricular myocytes

In the present study, we examined the effect of interleukin-2 (IL-2) on cardiomyocyte Ca(2+) handling. The effects of steady-state and transient changes in stimulation frequency on the intracellular Ca(2+) transient were investigated in isolated ventricular myocytes by spectrofluorometry. In the steady state (0.2 Hz) IL-2 (200 U/ml) decreased the amplitude of Ca(2+) transients induced by electrical stimulation and caffeine. At 1.25 mM extracellular Ca(2+) concentration ([Ca(2+)](o)), when the stimulation frequency increased from 0.2 to 1.0 Hz, diastolic Ca(2+) level and peak intracellular Ca(2+) concentration ([Ca(2+)](i)), as well as the amplitude of the transient, increased. The positive frequency relationships of the peak and amplitude of [Ca(2+)](i) transients were blunted in the IL-2-treated myocytes. The effect of IL-2 on the electrically induced [Ca(2+)](i) transient was not normalized by increasing [Ca(2+)](o) to 2.5 mM. IL-2 inhibited the frequency relationship of caffeine-induced Ca(2+) release. Blockade of sarcoplasmic reticulum (SR) Ca(2+)-ATPase with thapsigargin resulted in a significant reduction of the amplitude-frequency relationship of the transient similar to that induced by IL-2. The restitutions were not different between control and IL-2 groups at 1.25 mM [Ca(2+)](o), which was slowed in IL-2-treated myocytes when [Ca(2+)](o) was increased to 2.5 mM. There was no difference in the recirculation fraction (RF) between control and IL-2-treated myocytes at both 1.25 and 2.5 mM [Ca(2+)](o). The effects of IL-2 on frequency relationship, restitution, and RF may be due to depressed SR functions and an increased Na(+)-Ca(2+) exchange activity, but not to any change in L-type Ca(2+) channels.     

Decreased type VI adenylyl cyclase mRNA concentration and Mg(2+)-dependent adenylyl cyclase activities and unchanged type V adenylyl cyclase mRNA concentration and Mn(2+)-dependent adenylyl cyclase activities in the left ventricle of rats with myocardial infarction and longstanding heart failure.

OBJECTIVE: To address the effect of longstanding left ventricular (LV) hypertrophy and failure on LV adenylyl cyclase (AC) gene expression, mRNA concentrations of the main cardiac AC isoforms were measured in the non-infarcted area of LV from rats with myocardial infarction (MI), without (H) or with (F) LV failure, and in control (C) rats. Basal, GTP- and forskolin-stimulated Mg(2+)- and Mn(2+)-dependent AC activities were also measured in F and C rats. METHODS: Two- and six months after MI, steady-state AC mRNA concentrations were assessed by Northern blot analysis and RNase protection assay with isoform-specific cDNA and cRNA probes, respectively. AC activities were assessed on LV microsomal fractions using standard procedures. RESULTS: Types V and VI, and types IV and VII were the major and minor AC mRNA isoforms in both the LVs of F and C rats. Two months after MI, no difference in LV type V or VI mRNA to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA ratios was observed in rats with H or F compared to C. Six months after MI, no difference in LV type V mRNA concentration was observed between the three rat groups, whether this level was normalized to GAPDH, poly-(A+) or 18S RNAs. In contrast, a 35% decrease in the type VI mRNA to poly-(A+) RNA ratio and a 29% decrease in the type VI mRNA to 18S RNA ratio was observed only in rats with F compared to C (p < 0.05 vs. C for the two comparisons). Two- and six months after MI, basal and forskolin-stimulated Mg(2+)-dependent AC activities were decreased by 30-35% in F rats compared to C (p < 0.05), whereas Mn(2+)-dependent activities were unchanged. CONCLUSION: Longstanding LV hypertrophy and failure resulting from MI in rats is not associated with altered expression of the most abundant, type V, AC mRNA isoform, whereas that of type VI is decreased. The lack of change in Mn(2+)-dependent AC activities in the LV of F rats suggests that this decrease has no functional consequence on overall AC activity and that decreased Mg(2+)-dependent activities are related to alterations occurring upstream.     

Role of Ca2+-activated K+ channels on adrenergic responses of human saphenous vein

BACKGROUND: We studied the participation of K(+) channels on the adrenergic responses in human saphenous veins as well as the intervention of dihydropyridine-sensitive Ca(2+) channels on modulation of adrenergic responses by K(+) channels blockade. METHODS: Saphenous vein rings were obtained from 40 patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension. RESULTS: Iberiotoxin (10(-7) mol/L), an inhibitor of large conductance Ca(2+)-activated K(+) channels, and charybdotoxin (10(-7) mol/L), an inhibitor of both large and intermediate conductance Ca(2+)-activated K(+) channels, enhanced the contractions elicited by electrical field stimulation and produced a leftward shift of the concentration-response curve to norepinephrine. In contrast, the inhibitor of small conductance Ca(2+)-activated K(+) channels apamin (10(-6) mol/L) did not modify the contractile response to electrical field stimulation or norepinephrine. In the presence of the dihydropyridine Ca(2+)-channel blocker nifedipine (10(-6) mol/L), iberiotoxin and charybdotoxin failed to enhance the contractile responses to electrical field stimulation and norepinephrine. CONCLUSIONS: The results suggest that large conductance Ca(2+)-activated K(+) channels are activated by stimulation with norepinephrine to counteract the adrenergic-induced contractions of human saphenous vein. Thus, inhibition of these channels increases significantly the contraction, an effect that appears to be mediated by an increase in Ca(2+) entry through L-type voltage-dependent Ca(2+) channels.     

不同剂量维生素D3对心肌细胞电活动的影响

维生素D_可使豚鼠心室乳头肌细胞APA、OS、RP和Vmax降低,APD缩短,以APD50尤为明显,并随维生素D_3剂量增加而作用增强。该变化主要是通过细胞膜慢通道,使细胞内Ca~(2+)超负荷来实现的。     

Enhanced cardiac function in transgenic mice expressing a Ca(2+)-stimulated adenylyl cyclase

The predominant functional adenylyl cyclases normally expressed in cardiac tissue and coupled to beta-adrenergic receptors are inhibited by micromolar Ca(2+) concentration. To modify the overall balance of activities, we have generated transgenic mice expressing the Ca(2+)-stimulatable adenylyl cyclase type 8 (AC8) specifically in the heart. AC activity is increased by at least 7-fold in heart membranes from transgenic animals and is stimulated by Ca(2+) in the same range of concentration that inhibits the endogenous activity. Moreover, the in vivo basal protein kinase A activity was augmented 4-fold. Overexpression of AC8 in the heart has no detrimental consequences on global cardiac function. Basal heart rate and contractile function, measured by noninvasive echocardiography, were unchanged. In contrast, on release of parasympathetic tone, the intrinsic contractility is heightened and unresponsive to further beta-adrenergic receptor stimulation. AC8 transgenic mice thus represent an original model to investigate the relative influence of Ca(2+) and cAMP on cardiac function within a phenotype of enhanced cardiac contractility and relaxation.