钙通道,L型

摘要： 背景:肥胖与多种功能性胃肠病相关,肥胖者常存在胃肠动力障碍,且血清脂肪细胞因子内脏脂肪素(VF)水平明显升高.既往研究显示VF可抑制子宫、血管平滑肌收缩.目的:探讨VF对大鼠结肠平滑肌收缩的影响及其可能机制.方法:取正常Sprague-Dawley (SD)大鼠远端结肠制备成0.3 cm×0.8 cm的肌条,使用生物信号分析系统记录VF对肌条收缩活动的影响.体外培养SD乳大鼠结肠平滑肌细胞,予VF干预,以蛋白质印迹法检测肌球蛋白轻链(MLC)磷酸化水平和钙通道Cav1.2(α1亚基)表达;以激光共聚焦显微镜观察细胞外有或无Ca2+的情况下乙酰胆碱刺激引起的细胞内Ca2+浓度变化.结果:在肌条收缩实验中,VF(200 ng/mL)可显著减弱正常大鼠结肠平滑肌肌条的收缩张力(P＜0.05).在结肠平滑肌细胞实验中,VF(200 ng/mL)可下调Cav1.2通道表达,降低细胞内Ca2+浓度和MLC磷酸化水平(P＜0.05).结论:VF可能通过下调结肠平滑肌细胞膜Cav1.2通道表达降低细胞内Ca2+浓度,引起结肠平滑肌收缩障碍,从而参与结肠动力障碍的发生.

摘要： 目的 探讨β3肾上腺素能受体(β3-AR)对慢性心力衰竭(CHF)大鼠左心房肌L型Ca2+通道亚单位α2δ-2编码基因CACNA2D2的调控是否与微小RNA(miRNA)-1及miRNA-328存在关联.方法 22只雄性Wistar大鼠随机选6只为正常对照组(NC组),另16只采用皮下注射异丙肾上腺素建立CHF动物模型,将存活的12只大鼠再随机分为CHF组6只和BRL组(在大鼠尾静脉注射β3-AR特异性激动剂BRL-37344)6只.采用超声心动图检测大鼠左心房内径(LAD)、左心房射血分数(LAEF)及LVEF.采用苏木精-伊红染色检测大鼠左心房肌病理学变化.采用实时荧光定量PCR检测大鼠左心房肌β3-AR、CACNA2D2以及miRNA-1、miRNA-328表达水平.结果 BRL组大鼠LAD显著大于NC组和CHF组[(4.42±0.15)mm vs (3.50±0.21)mm和(4.09±0.17)mm,P＜0.01];BRL组LAEF显著低于NC组和CHF组[(34.91±1.51)％ vs (59.89±3.17)％和(40.09±0.95)％,P＜0.01].与CHF组比较,BRL组大鼠左心房肌细胞水肿进一步加重,可见明显肥大细胞等病理学改变更显著.与NC组比较,CHF组大鼠左心房肌ββ3-AR、CACNA2D2、miRNA-1及miRNA-328表达上调(P＜0.01);与CHF组比较,BRL组大鼠左心房肌β3-AR、CACNA2D2、miRNA-1及miRNA-328表达进一步上调(P＜0.01).miRNA-1、miRNA-328、CACNA2D2与β3-AR表达呈正相关(r=0.870、0.904、0.911,P＜0.01);CACNA2D2与miRNA-1、miRNA-328表达呈正相关(r =0.880、0.954,P＜0.01).结论 β3-AR对左心房CACNA2D2的正性调控可能与miRNA-1、miRNA-328存在关联.

摘要： [目的] 探讨在吗啡引起的痛觉超敏状态下,SD大鼠延髓头端腹内侧区电压门控钙通道(voltage-gated calcium channels, VGCCs)蛋白的表达变化和功能变化.[方法] 采用western blot方法检测α1C和α1H亚基蛋白在大鼠延髓头端腹内侧区(the rostral ventromedial medulla,RVM)的表达,采用脑片全细胞膜片钳技术记录大鼠RVM神经元的VGCCs电流.[结果] 在吗啡诱导的痛觉超敏状态下,SD大鼠RVM的α1C亚单位蛋白表达显著增加,同时神经元的VGCCs总电流和L-型VGCCs电流也显著增加.[结论] 延髓RVM的L-型电压门控钙通道的可塑性变化,可能是导致吗啡痛觉超敏的重要原因.%[Objective]To investigate the changes of voltage-gated calcium channels (VGCCs) in the rostral ventromedial medulla of SD rats under morphine-induced hyperalgesia.[Methods]The expression of a1C and a1H subunit proteins in the rostral ventromedial medulla (RVM) was detected by western blot.The VGCCs current of RVM neurons was recorded by the whole-cell patch-clamp technique.[Results]Our results indicated that the expression of α1C subunit in the RVM significantly increased under morphine-induced hyperalgesia, which was followed by the significant increase in total VGCCs currents and L-type VGCCs currents.[Conclusion]This data implicates that α1C-subunit-containing L-type VGCCs in RVM may play an essential role as a cellular mechanism leading to hyperalgesia.

摘要： Objective To explore the effects of L⁃type calcium channel (LTCC) α1C and β3 subunits on that magnesium inhibited thoracic aortic calcification induced by β⁃glycerophosphate (β⁃GP). Methods Vascular smooth muscle cells (VSMCs) and aortic rings from rat aortic were cultured, then divided into control group, high phosphorus group (10 mmol/L β⁃GP), magnesium group (10 mmol/L β⁃GP+3 mmol/L MgSO4) and 2⁃APB (an inhibitor of magnesium transporter) group (10 mmol/L β⁃GP+3 mmol/L MgSO4+0.1 mmol/L 2⁃APB). Calcium deposition of VSMCs and aortic rings were respectively measured by alizarin red staining and Von Kossa staining, meanwhile the quantification of their calcium was tested by OCPC. The mRNA expressions of Runx2, LTCCα1C andβ3 in VSMCs were detected by RT⁃PCR, and their protein expressions were detected by Western blotting. Intracellular calcium ion of VSMCs was tested by fluorescence probe and alkaline phosphatase (ALP)activity was measured by ELISA. The Runx2 expression of aortic rings was detected by immunohistochemistry. Results After VSMCs stimulated for 7 days, calcium, ALP, mRNA and protein expressions of LTCCα1C, LTCCβ3 and Runx2, and intracellular calcium ion in high phosphorus group were higher than those in control group (all P0.05). Conclusion Magnesium may down⁃regulate expressions of LTCCα1C andβ3 subunit, prevent calcium influx and then inhibit osteogenic differentiation so as to reduce β⁃glycerophosphate⁃induced VSMCs calcification.%目的：探讨L型钙通道（L⁃type calcium channel ，LTCC）α1C、β3亚基在镁抑制高磷诱导的大鼠血管平滑肌细胞（VSMC）钙化中的作用。方法体外原代培养大鼠胸主动脉VSMC和血管环，用β⁃甘油磷酸盐（β⁃glycerophosphate ，β⁃GP）诱导钙化。将细胞、血管环分别分为4组培养7 d：正常对照组、高磷组（10 mmol/Lβ⁃GP）、镁干扰组（10 mmol/Lβ⁃GP+3 mmol/L MgSO4）、镁通道抑制剂（2⁃APB）组（10 mmol/Lβ⁃GP+3 mmol/L MgSO4+0.1 mmol/L 2⁃APB）。采用茜素红染色、硝酸银染色分别检测各组VSMC、血管环的钙盐沉积情况，且用邻甲酚酞络合酮比色法检测钙含量。反转录PCR、Western印迹检测VSMC中LTCCα1C、β3亚基，Runx2的基因和蛋白表达。免疫组织化检测各组血管环中Runx2蛋白表达。ELISA测定VSMC碱性磷酸酶（ALP）活性，荧光探针法测定细胞内钙离子浓度。结果与正常对照组比较，高磷组VSMC钙含量，ALP活性，LTCCα1C、LTCCβ3和Runx2 mRNA和蛋白的表达，胞内钙离子浓度均增加（均P＜0.05）；与高磷组比较，镁干扰组VSMC钙含量，ALP活性，LTCCα1C、LTCCβ3和Runx2 mRNA和蛋白的表达，钙离子浓度均降低（均P＜0.05）。镁干扰组血管环组织钙含量和Runx2蛋白表达均低于高磷组（均P＜0.05）。镁通道抑制剂组以上各项目与高磷组比较差异均无统计学意义。结论镁可以抑制高磷诱导的大鼠血管钙化，其可能是通过抑制LTCCα1C和β3亚基表达，阻滞VSMC钙离子内流，降低Runx2的表达，从而抑制VSMC发生表型转化实现的。

摘要： 目的 探讨心房颤动(房颤)射频消融术是否通过对调控离子通道蛋白的微小RNA(microRNA,miRNA)的影响,实现心房离子流再平衡和逆重构,并试图发现有价值的调控miRNA.方法 选择行房颤射频消融术患者(阵发性、持续性和永久性房颤各10例)30例作为房颤组,健康体检者10例作为正常对照组.正常对照组体检时,房颤组射频消融术前和术后3个月分别取外周血,使用miRNA芯片(miRNA v18.0)进行全基因组miRNA表达谱微阵列分析,2组miRNA表达比值≥1.5倍为显著上调,实时定量PCR验证miRNA表达差异结果,并通过mirbase、miranda、targetscan数据库进行靶基因分析.结果 与正常对照组比较,房颤组射频消融术前主要参与离子通道蛋白调控的21个miRNA差异表达均有显著意义(P＜0.01);房颤组术后3个月与自身术前比较,上述21个miRNA表达亦有明显差异(P＜0.01).其中miR-1266等5个miRNA术前表达上调≥1.5倍,术后明显下调≥10倍;仅miR-3664-5p术前下调8.88倍,术后进一步下降46.06倍;其余15个miRNA均术前表达下调,术后显著上调.结论 房颤射频消融术通过影响调控离子通道蛋白的主要miRNA,实现了心房离子流逆重构.调控多个离子流的miR-1266,miR-377-5p,miR-101-5p和miR-151-3p有望成为房颤治疗新靶点.

摘要： Objective To explore the effect and possible mechanisms of acidification on high phosphorus induced vascular smooth muscle cells (VSMCs) calcification in rats. Methods VSMCs were isolated from rat aorta, identified by immunocytochemistry, and randomly divided into control group and high phosphorus group according to the pH, the high phosphorus group was further settled into three subgroups, high phosphorus + pH6. 8, + pH7. 1 and + pH7. 4, which were treated with β-glycerophosphate, and acidified by HCL to adjust the pH respectively. The VSMC mRNA expressions of L-type calcium channel (LTCC) subunitsα1C , β2 , β3 , Runt-related transcription factor 2 ( Runx2) and Smad1 mRNA were detected by RT-PCR after stimulated for 4 days; meanwhile, the VSMCs were loaded with calcium probe Fluo-3 / AM, and the concentration of calcium was measured by Fluo-3 / AM among different groups. The activity of alkaline phosphatase and calcium deposition were tested after culturing 14 days. Results Compared with control group, calcium concentration and the activity of ALP in VSMCs were significantly increased in high phosphorus + pH7. 4 group after incubation for 14 days (88. 26 ± 6. 43 vs. 22. 39 ± 3. 19, 94. 33 ± 3. 08 vs. 20. 39 ± 1. 18, both P ﹤ 0. 05), the expression of Smad1, Runx2 and LTCC β3 subunit mRNA in high phosphorus + pH7. 4 group was increased as well (0. 65 ± 0. 05 vs. 0. 07 ± 0. 01, 0. 37 ± 0. 02 vs. 0. 01 ± 0. 00, 0. 80 ± 0. 01 vs. 0. 34 ± 0. 13, all P ﹤ 0. 05). Besides, Smad1, Runx2 and LTCCβ3 subunit mRNA were decreased in high phosphorus + pH7. 1 group and high phosphorus + pH6. 8 group (0. 25 ± 0. 02 vs. 0. 37 ± 0. 02, 0. 09 ± 0. 01 vs. 0. 37 ± 0. 02, 0. 44 ± 0. 04 vs. 0. 65 ± 0. 05, 0. 23 ± 0. 01 vs. 0. 65 ± 0. 05, 0. 64 ± 0. 11 vs. 0. 80 ± 0. 01, 0. 43 ± 0. 01 vs. 0. 80 ± 0. 01, all P ﹤ 0. 01), compared with those in high phosphorus + pH7. 4 group as the pH decreased. There was no significant difference in LTCC α1C and β2 subunits mRNA among each groups (P = 0. 08, P = 0. 74). Calcium influx in VSMCs was partially blocked as pH was changed ( P ﹤ 0. 01) . Conclusions Acidic environment can inhibit high phosphorus induced rat VSMCs calcification, its mechanism is possibly by downregulation of LTCC β3 subunit gene expression, decreasing calcium ion influx and preventing VSMC phenotypic transformation to achieve.%目的：探讨酸性环境对高磷诱导的大鼠血管平滑肌细胞(VSMCs)钙化的影响及可能机制。方法体外分离培养大鼠 VSMCs,采用免疫细胞化学方法鉴定。将 VSMCs 按随机数字表法分为正常对照组、高磷+ pH7.4、高磷+ pH7.1和高磷+ pH6.8(在高磷培养基的基础上调整 pH 值为6.8、7.1和7.4三个亚组)。刺激4 d 后,采用 RT-PCR 检测 L 型钙通道(LTCC)α1C、β2和β3亚基, Runt 相关转录因子2(Runx2)及 Smad1基因的表达；应用钙离子探针 Fluo-3/ AM 检测 VSMCs 胞外钙离子内流的效应变化。刺激14 d 后,对各组细胞进行钙化染色、钙含量和碱性磷酸酶(ALP)活性测定。结果与正常对照组比较,高磷+ pH7.4组钙含量、ALP 活性、Runx2和 Smad1mRNA 的表达明显增高(88.26±6.43比22.39±3.19、94.33±3.08比20.39±1.18、0.37±0.02比0.01±0.00、0.65±0.05比0.07±0.01,均为 P ﹤0.05)；与高磷+ pH7.4组比较,高磷+ pH7.1组和高磷+ pH6.8组的钙含量、ALP 活性、Runx2和 Smad1mRNA 的表达均降低(69.95±1.72和50.74±3.29、51.11±2.05和34.62±1.13、0.25±0.02和0.09±0.01、0.44±0.04和0.23±0.01,均为 P ﹤0.05)。与正常对照组比较,高磷+ pH7.4组的 LTCCβ3亚基 mRNA 表达水平增加(0.80±0.01比0.34±0.13, P ﹤0.01),高磷+ pH7.1组和高磷+ pH6.8组的 LTCCβ3亚基 mRNA 表达水平均下降(0.64±0.11和0.43±0.01,均为 P ﹤0.01)。各组之间 LTCCα1C 和β2亚基 mRNA 的表达差异无统计学意义(P =0.08和0.74)。与正常对照组比较,高磷+ pH7.4组的 VSMCs 胞内钙离子浓度增加(438.33±7.50比149.54±20.89,P ﹤0.05)；高磷+ pH7.1组和高磷+ pH6.8组的 VSMCs 胞内钙离子浓度均降低(329.66±16.64和234.00±17.43,均为 P ﹤0.01)。结论酸性环境可以抑制高磷诱导的大鼠VSMCs 钙化,其可能是通过抑制 LTCC β3亚基表达,降低 VSMCs 钙离子内流,阻滞 VSMCs 发生表型转化来实现的。

摘要： 目的 探讨miRNA-377(miR-377)与房颤相关离子通道蛋白的靶向调控关系.方法 实验分为过表达组、干扰组、阴性组和空白组.将L型钙离子通道α1C亚单位(CACNA1C)的重组荧光素酶报告质粒与miR-377模拟体及阴性对照共转染于人胚胎肾HEK293细胞,检测各组荧光素酶的相对活性.将miR-377模拟体、干扰体及阴性对照导入大鼠胚胎心肌H9C2细胞,观察其对靶基因的表达和功能调控.结果 与阴性组比较,过表达miR-377组CACNA1C荧光素酶相对活性降低31％(0.316±0.006 vs 0.455±0.008,P=0.009),过表达组及干扰组CACNA1C、CACNB2基因mRNA表达水平无明显变化.miR-377模拟体转入H9C2细胞可抑制CACNA1C蛋白表达(P＜0.05),降低L型Ca电流的密度,使其峰值密度从-3.23±0.64pA/pF降至-2.26±0.16pA/pF(P＜0.05).结论 CACNA1C基因可能是miR-377的直接靶基因,miR-377可能通过抑制CACNA1C的表达从而降低L型钙电流来参与房颤电重构,有可能成为房颤干预治疗的靶点.

摘要： Objective To evaluate the role of calcium channel in the mechanism of the generation and maintenance of bursting firing of substantia nigra pars compacta (SNc) dopaminergic neurons in rats.Methods Using the patch clamp technique,we observed the firing pattern switching features after adding 10 μmol/L N-methyl-D-aspartic acid (NMDA),compared the changes of whole-calcium current and L-type calcium current with or without NMDA,and analyzed the correlation between the generation of burst firing and L-type calcium channel activation.Results After NMDA treatment,the firing pattern of SNc dopaminergic neurons changed to burst firing,which was compromised by a charastistic high plateau potential and series of action potential on it.The current density of L-type calcium current increased significantly after adding NMDA,which,from (2.86 ±0.26) pA/pF (n =28),significantly increased to (3.75 ± 0.18) pA/pF (n =34 ; t =7.52,P =0.002 8).The high plateau potential was almost abolished with the application of verapamil,a specific antagonist of L-type calcium channel.Consiusion NMDA could induce the firing pattern changed to burst firing in SNc dopaminergic neurons,while L-type calcium channel contributes to the process of generation and maintenance of burst firing.%目的 研究钙离子通道对大鼠黑质致密部(SNc)多巴胺能神经元暴发式放电模式产生和维持的机制.方法 应用全细胞膜片钳的方法,施加N-甲基-D-天冬氨酸(NMDA)诱导神经元放电模式转变,观察并记录其相应放电模式的特点,记录并比较加入10 μmol/L NMDA前后全钙离子流和L-钙电流的变化情况,通过外液加入河豚毒素、维拉帕米、氯化镍后,分析暴发式放电产生和维持与L-钙通道激活之间的联系.结果 加入NMDA后神经元放电模式转变为暴发式放电,该暴发式放电为平台电位及其上的动作电位构成;L-钙通道电流密度峰值在加入NMDA后明显增加,从(2.86±0.26) pA/pF(n =28)增加到(3.75 ±0.18) pA/pF(n =34),差异具有统计学意义(t=7.52,P=0.0028);采用L-钙阻断剂维拉帕米后暴发式放电中的平台电位几乎消失.结论 NMDA能够诱导SNc多巴胺能神经元转变为暴发式放电模式,而L-钙通道参与暴发式放电产生和维持的过程.

摘要： ObjectiveTo determine the levels of expressions of L-type calcium channel α1C subunit(Cav1.2) in the atrial myocardium of rats with insulin resistance(IR), and the effect of telmisartan on the Cav1.2 expression.MethodsThirty-two IR OLETF rats ware randomly divided into two groups of 16: IR model group (group M); IR+telmisartan (5 mg·kg-1·d-1) group (group T) for twenty weeks. Sixteen LETO rats were the normal control group (group N). The plasma levels of fasting insulin(FINS), fasting blood glucose(FBG), serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol(LDL-C) were detected in three groups, and HOMA-IR was measured; the expression levels of Cav1.2 in atrium sinistrum tissue were measured by Western Blotting technique.Results Compared with group N, FBG, TC, TG, LDL-C, FINS and HOMA-IR were significantly increased (P<0.05), while the HDL-C level was significantly decreased (P<0.05), atrial muscle Cav1.2 expression levels were significantly lower in group M(P<0.05); compared with group M, FBG, TC, TG, LDL-C, FINS and HOMA-IR were obviously decreased (P<0.05), and the level of HDL-C had no significant changes (P=0.384), atrial muscle Cav1.2 expression level increased in group T (P<0.05). ConclusionThese data indicate that the atrial myocardium Cav1.2 is down-regulated in IR rats; after telmisartan intervention, the expression level of atrial myocardium Cav1.2 increase in IR rats.%目的：探讨胰岛素抵抗（IR）大鼠心房肌L型钙通道α1C亚单位（Cav1.2）的表达水平以及替米沙坦对其表达的影响。方法32只IR OLETF大鼠随机分为2组，每组16只：IR模型组（M）；IR+替米沙坦（5 mg·kg-1·d-1）组（T）。LETO大鼠16只为对照组（N）。20周后测定3组大鼠的血清胰岛素（FINS）、空腹血糖（FBG）、血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C），并计算胰岛素抵抗指数（HOMA-IR）；用Western blot技术检测心房肌中Cav1.2的表达。结果与N组相比，M组FBG、TC、TG、LDL-C、FINS及HOMA-IR水平明显增高（P＜0.05），而HDL-C水平明显降低（P＜0.05），心房肌中Cav1.2表达水平明显降低（P＜0.05）；与M组相比，T组FBG、TC、TG、LDL-C、FINS及HOMA-IR水平明显降低（P＜0.05），而HDL-C水平无明显变化（P＝0.384），心房肌中Cav1.2表达水平明显升高（P＜0.05）。结论 IR大鼠心房肌中Cav1.2表达降低；经替米沙坦干预后，IR大鼠心房肌中Cav1.2的表达水平回升。

摘要： Objective To investigate the expression of α1D subunit of L-type calcium channels (Cav1.3) in C57BL/6 mice cochlea and its correlation with presbycusis.Methods Auditory function was measured with auditory brainstem response(ABR) in C57BL/6 mice at 4,14,24 and 48 weeks.Morphological changes of the inner ear were studied by using hematoxylin and eosin staining.The expression of Cav1.3 channels was detected by immunofluorescence and the expression of CACNA1D mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR).Results Immunofluorescence photographs revealed that Cav1.3 channels were mainly localized in the hair cell,spiral ganglion cell,spiral ligment,stria vascularis,spiral limbus.The ABR threshold at click(27.08±9.19) dB SPL,4 KHz(23.79± 13.31)dB SPL,8 KHz(18.83± 12.18)dB SPL,was higher in 14-,24-,and 48-week group than in 4-week group (all P＜0.05).The ABR threshold at click(87.81±8.36)dB SPL,4KHz(85.63±9.88)dB SPL,8KHz(79.50±9.83) dB SPL,was significantly higher in 48-week group than in 4-,14-,24-week groups (all P＜0.01).Along with aging,the missing hair cells and spiral ganglion cells were increased,stria vascularis and spiral ligament were atrophied in a certain degree,and the expression of Cav1.3 channels was gradually decreased (4 weeks 218.94 ± 11.29 ; 14 weeks 184.67 ± 11.92 ; 24 weeks 148.18 ± 8.35 ; 48 weeks 98.04±4.52; all P＜0.01).Conclusions The expression of Cav1.3 channels is decreased along with age.Dysfunction or missing of Cav1.3 calcium channels may be related to presbycusis.%目的 研究L型钙离子通道蛋白α1D亚基(Cav1.3)在老年性耳聋小鼠耳蜗组织中的表达和意义. 方法 应用听性脑干反应(ABR)分别检测4、14、24、48周龄的C57BL/6小鼠的听力,苏木素-伊红(HE)染色观察内耳形态的变化.免疫荧光方法观察Cav1.3在内耳组织中的分布,同时采用反转录聚合酶链反应(RT PCR)检测其基因CACNA1D在内耳组织的mRNA表达. 结果 Cav1.3主要分布在小鼠耳蜗内外毛细胞、螺旋神经节、螺旋韧带、血管纹、螺旋(板)缘细胞.与4周龄小鼠比较,[短声(27.08±9.19)dB SPL、4 KHz(23.79±13.31)dB SPL、8 KHz(18.83±12.18)dB SPL],14、24、48周龄ABR反应阈值提高(F=95.86,P＜0.05);48周龄小鼠ABR反应阈值[短声(87.81±8.36)dB SPL、4 KHz(85.63±9.88)dB SPL、8 KHz(79.50±9.83) dB SPL],较4、14、24周龄大鼠均提高(F=115.97,P＜0.01).随着鼠龄的增长,内耳毛细胞和螺旋神经节细胞逐渐出现缺失;血管纹和螺旋韧带也呈现萎缩;Cav1.3表达含量逐渐减少,4周218.94±11.29,14周184.67±11.92,24周148.18±8.35与48周98.04±4.52比较,差异有统计学意义(F=119.17,P＜0.01).结论 老年性耳聋小鼠Cav1.3钙离子通道蛋白表达含量随年龄增长而减少,其功能的异常和缺失可能在老年性耳聋的发病中起一定作用.

摘要： 本发明公开了一种针对人血管平滑肌细胞L型钙通道和血管紧张素1型受体的嵌合型二价降压疫苗及其应用，它包括由180个或者240个重组乙肝核心蛋白单体分子自我组装形成的二十面体病毒样颗粒，所述重组乙肝核心蛋白单体分子以免疫原性载体为骨架+高血压发病相关靶分子表位组合。本发明根据乙肝核心抗原的分子结构及免疫学特性，结合目前高血压疫苗研制的实际缺陷，设计出了一种针对多靶点的治疗性降压疫苗，该疫苗能诱导产生分别针对多种治疗性靶点的特异性抗体，发挥联合降压效应，有效降低了高血压动物模型的血压。

摘要： 本发明公开了一种人血管平滑肌细胞L型钙通道免疫原性肽段及其疫苗和应用，所述人血管平滑肌细胞L型钙通道免疫原性肽段为以下四种肽段中任意一种，它们的氨基酸序列分别为VPAEDDPSPC、DSSKQTEAECK、DSHTEDKGPI和CAPESEPSNSTE。将该血管平滑肌细胞L型钙通道免疫原性肽段与重组Qβ‑2aa噬菌体病毒样颗粒蛋白耦联结合，在病毒样颗粒表面重复、有序排列，以形成多肽‑载体疫苗。公开了该疫苗在治疗原发性高血压方面的应用。该疫苗能够在实验动物体内诱导产生高效价的特异性抗体，能够显著降低自发性高血压大鼠的血压。

摘要： 本发明涉及一种药物组合，其包含：第一活性成分，该第一活性成分为N‑[1‑(5‑氰基‑吡啶‑2‑基甲基)‑1H‑吡唑‑3‑基]‑2‑[4‑(1‑三氟甲基‑环丙基)‑苯基]‑乙酰胺或其医药学上可接受的盐；及具有抗癫痫效果的第二活性成分或其医药学上可接受的盐。

摘要： 本发明公开了一种甲氧喹酸在制备用于治疗和/或预防以T‑型钙通道为治疗靶点的疾病的药物中的应用。本发明公开了甲氧喹酸的新用途，为开发用于治疗和/或预防以T‑型钙通道为治疗靶点的疾病的药物提供了新的理论和技术支撑，在临床治疗领域具有广泛的应用前景。

摘要： 本发明涉及式(I)化合物，

摘要： 本发明是关于式(I)化合物

摘要： 金丝桃素对T－型钙通道活性有特殊的抑制效果。含金丝桃素的金丝桃提取物也可抑制T－型钙通道活性。此外,金丝桃提取物中的其它化学物质对金丝桃素有协同作用。基于此,金丝桃素或含金丝桃素的金丝桃提取物可用作T－通道的阻断剂。金丝桃提取物,金丝桃属的其它物种的提取物,含金丝桃素的其它植物的提取物,金丝桃素的衍生物,金丝桃素的类似物如假金丝桃素,和其它金丝桃提取物组分可以用于针对T－型钙通道的疗法,用于与T－型通道畸变有关的疾病的治疗。提供了使用金丝桃素和金丝桃提取物的方法。

摘要： 本发明公开了一种针对人血管平滑肌细胞L型钙通道和血管紧张素1型受体的嵌合型二价降压疫苗及其应用，它包括由180个或者240个重组乙肝核心蛋白单体分子自我组装形成的二十面体病毒样颗粒，所述重组乙肝核心蛋白单体分子以免疫原性载体为骨架+高血压发病相关靶分子表位组合。本发明根据乙肝核心抗原的分子结构及免疫学特性，结合目前高血压疫苗研制的实际缺陷，设计出了一种针对多靶点的治疗性降压疫苗，该疫苗能诱导产生分别针对多种治疗性靶点的特异性抗体，发挥联合降压效应，有效降低了高血压动物模型的血压。

摘要： 本发明提供了对PDE－3和L－型钙通道具有抑制活性的化合物。本发明还提供了包含此化合物的药用组合物和使用此化合物治疗心血管疾病、中风、癫痫症、眼睛疾病或偏头痛的方法。

摘要： 本文部分地描述了可用于预防和/或治疗与异常T‑型钙通道的功能有关的疾病或病症的剂型和组合物，所述疾病或病症是诸如癫痫和癫痫综合征(例如，失神性癫痫发作、青少年肌阵挛型癫痫或遗传性癫痫)、震颤(例如，特发性震颤)和精神病学障碍(例如，心境障碍(例如，严重抑郁障碍))。本发明还包括用于调节T‑型钙通道的功能的方法。