慢性心房颤动对人心房肌钙/钙调素依赖性蛋白激酶Ⅱ表达的影响

目的：探讨慢性心房颤动(房颤)对人心房肌细胞内游离Ca2+浓度及心肌组织钙/钙调素依赖性蛋白激酶Ⅱ (CaMKⅡ)表达的影响。 方法: 用激光共聚焦显微镜技术，对急性分离的慢性风湿性心脏病伴慢性房颤或窦性心律患者的心房肌细胞内游离Ca2+浓度进行测定，同时用Western blotting法检测心房肌组织CaMKⅡ表达的变化。 结果: 慢性风湿性心脏病伴慢性房颤患者心房肌细胞内游离Ca2+浓度显著高于窦性心律患者［(276.38±38.12）nmol/L vs （122.28±45.63)nmol/L, P<0.05］。慢性风湿性心脏病伴慢性房颤患者心房肌CaMKⅡ的表达明显强于窦性心律患者（10.14±0.31 vs 6.86±0.89， P<0.05）。 结论: 慢性房颤患者心房肌细胞内存在钙超载，Ca2+/CaMKⅡ信号转导途径可能是维持慢性房颤重要的病理生理基础之一。     

慢性房颤患者心房肌细胞乙酰胆碱敏感钾通道的研究

目的： 研究慢性房颤时乙酰胆碱敏感钾通道电流及其基因表达的变化，探讨该离子通道变化在房颤发生与发展中的作用。 方法： 膜片钳全细胞技术记录风湿性心脏病慢性房颤患者和窦性心律患者心房肌细胞乙酰胆碱敏感钾通道电流，分析两组的电流密度-电压关系曲线；半定量逆转录聚合酶链式反应(RT-PCR)测量心房肌细胞乙酰胆碱敏感钾通道基因(Kir3.4)mRNA表达的变化。 结果： （1）与窦性心律组比较，在测试电位-80 mV--120 mV时，慢性房颤组心房肌细胞乙酰胆碱敏感钾通道电流密度明显减小。其中测试电位为 -100 mV 时，慢性房颤组电流密度为(-11.665±1.027)pA/pF(n=11)，窦性心律组为(-19.486±0.766) pA/pF(n=11) (P<0.01)。（2）慢性房颤组心房肌细胞Kir3.4 mRNA表达低于窦性心律组54.3%，为0.523±0.301(n=11) vs 0.239±0.102 (n=11), P＜0.01。 结论： 慢性房颤时乙酰胆碱敏感钾通道电流密度的改变与乙酰胆碱敏感钾通道基因表达下调呈正相关，该通道的改变可能与房颤的发生和发展有关。     

兔膈肌肌浆网Ca2+-ATPase活性及钙离子的转运

本文分别用定磷法测定兔膈肌SR Ca 2 -APTase 活性、Fura-2 荧光法测定SR Ca 2 释放、摄取动力学和[ 3 H] -Ryanodine 与RyR 结合实验测定SR RyR 的量,分析其功能特性。 结果显示兔隔肌、心肌和骨骼肌SR Ca 2 -APTase 活性分别为70.13 ±8.25、 41.25 ±6.25 和120.17± 17.03 m mol/L pi/mg 蛋白/h1 。膈肌的SRCa 2 -APTase 活性显著高于心肌P<0.01 。但明显低于骨骼肌P<0.01; 膈肌SR Ca 2 释放量和摄取速度显著快于心肌（P<0.01）,但明显低于骨骼肌（P<0.01）;膈肌SR RyR 同[ 3 H] Ryanodine 的最大结合值（Bmax）是0.78 ±0.05pmol/mg 蛋白,其解离常数（KD）是6.93 1.13nmol/L,分别位于心肌和骨骼肌范围内。本文认为膈肌Ca 2 释放单位、SR Ca 2 -APTase 和SR Ca 2 释放摄取动力学分别具有心肌和骨骼肌的一些特征,其Ca 2 释放可能具有变构偶联和CICR 偶联两种形式,心肌型DHPR 亚型,RyR 3 和SERCA 2 a 的存在可能是膈肌ECC 依赖于细胞外Ca 2 的主要原因。     

腺相关病毒载体介导的PLB基因反义RNA对大鼠心肌细胞肌浆网Ca2+-ATPase活性和［Ca2+］i的作用

目的：探讨腺相关病毒载体介导的磷酸受纳蛋白（PLB）反义RNA对肌浆网Ca2+-ATPase活性以及细胞内钙浓度（［Ca2+］i）的作用。 方法： 构建PLB反义RNA的重组腺相关病毒载体（rAAV-asPLB）和携带报告基因LacZ的重组腺相关病毒载体（rAAV-LacZ）。分别转染培养的大鼠心肌细胞，测定PLB mRNA和蛋白质表达，检测肌浆网Ca2+-ATPase活性和［Ca2+］i。 结果： RT-PCR和Western blotting显示，感染rAAV-asPLB的心肌细胞的PLB mRNA和蛋白质表达低于正常对照和感染rAAV-LacZ组；而Ca2+-ATPase活性大于正常对照和感染rAAV-LacZ组。激光共聚焦显微镜检测显示，静息状态时，rAAV-asPLB感染组［Ca2+］i降低；异丙肾上腺素刺激后，各组［Ca2+］i均升高，但是rAAV-asPLB感染组［Ca2+］i变化幅度大。 结论： 腺相关病毒介导的PLB反义RNA对大鼠心肌细胞PLB表达具有抑制作用，增强Ca2+-ATPase活性，降低静息状态的［Ca2+］i ，增加异丙肾上腺素刺激后［Ca2+］i 的变化幅度。     

周围神经损伤后脊髓前角运动神经元内游离Ca2+的浓度

背景：神经损伤后可引起细胞膜上Ca²⁺通道的开放,使细胞外Ca²⁺内流,造成细胞内的钙超载。 目的：观察臂丛神经根切断伤后相应脊髓前角运动神经元内游离Ca²⁺浓度的变化。 方法：健康成年雄性Wistar大鼠84只,分为3组：假手术组暴露臂丛神经不切断;对照组臂丛神经切断伤后不做其他处理;实验组臂丛神经切断伤后,给予腹腔注射Ca2+阻带剂维拉帕米4 mg/(kg•d)。于切断伤后12 h,24 h,48 h,72 h,1周,2周,4周每组随机以4只取材。 结果与结论：周围神经损伤开始,对照组及实验组大鼠损伤侧脊髓前角运动神经元细胞内Ca²⁺浓度开始升高,至伤后48 h达高峰,此后逐渐下降,伤后1周,实验组已基本回至正常水平,但仍较假手术组高。说明神经损伤后相应神经元细胞膜上L型Ca²⁺通道开放,Ca2+内流进入细胞内,导致神经细胞内游离Ca²⁺浓度增加,L型Ca²⁺通道可以被维拉帕米阻断,减少神经损伤后的Ca²⁺内流,减少神经细胞凋亡的数量。     

β2肾上腺素受体拮抗剂对大鼠心肌梗死后心肌细胞胞浆游离Ca2+浓度的影响

目的：观察β2肾上腺素受体拮抗剂对心肌梗死后心肌细胞胞浆游离Ca2+浓度(［Ca2+］i)的影响。 方法： 结扎冠状动脉，复制大鼠心肌梗死模型。随机分为心肌梗死后2、4、8周组，正常对照组作假手术。分离大鼠心肌细胞，每组大鼠制备20份样品，再随机分为4小组，分别给予β2受体拮抗剂ICI118,551、β1受体拮抗剂阿替洛尔、非选择性β受体拮抗剂普萘洛尔后，用Fura-2荧光技术测定心肌细胞［Ca2+］i。 结果： 心肌梗死后4、8周，ICI118,551组心肌细胞［Ca2+］i增幅显著低于异丙肾上腺素组(24.5%±5.7% vs 57.8%±13.2%, P<0.01; 12.2%±7.9% vs 44.6%±11.3%,P<0.01)；正常对照组和心肌梗死后2周，上述两组心肌细胞［Ca2+］i增幅无显著差异(P>0.05)。正常对照组和心肌梗死后2周，阿替洛尔组心肌细胞［Ca2+］i增幅显著低于异丙肾上腺素组(P<0.05)；正常对照组及心肌梗死后2、4、8周,普萘洛尔组心肌细胞［Ca2+］i增幅均显著低于异丙肾上腺素组（P<0.05）。 结论： β2受体拮抗剂对于有效抑制心肌梗死后交感神经激动引起的心肌细胞内钙超载可能起重要作用。     

PAR-2激动剂对肝癌细胞增殖及Ca2+水平的影响

目的： 研究PAR-2激动剂对人肝癌HepG2细胞增殖及细胞内Ca2+浓度（［Ca2+］c）的影响。方法: 培养人肝癌细胞HepG2, 分别利用PAR-2激动剂SLIGKV-NH2及反PAR-2激动肽VKGILS-NH2干预肝癌细胞生长,用Fura-2荧光法测定肝癌细胞内［Ca2+］c,用MTT法检测对肝癌细胞增殖能力的影响,流式细胞术（FCM）检测细胞周期改变情况,RT-PCR法检测cyclinD1 mRNA表达变化。结果: 50 μmol/L SLIGKV-NH2刺激HepG2细胞后,［Ca2+］c迅速短暂升高（P<0.01）;G0/G1期比例明显降低,S期和G2/M期细胞比例和细胞增殖指数(PI)明显提高（P<0.01）;cyclinD1 mRNA的表达显著增加（P<0.01）。SLIGKV-NH2在1-50 μmol/L时可以促进HepG2细胞增殖,呈剂量依赖性（P<0.01或P<0.05）。而VKGILS-NH2组与对照组相比差异无显著（P>0.05）。结论: PAR-2激动剂在体外能通过激活PAR-2,诱导HepG2细胞内［Ca2+］c升高,上调cyclinD1 mRNA的表达,加速HepG2细胞周期进程,促进DNA合成,促进肝癌细胞增殖。     

心房颤动患者心房Ⅰ型胶原重构与左心房扩大

目的：探讨心房颤动患者心房Ⅰ型胶原重构与左心房扩大在房颤发病机制中可能的作用以及它们之间的关系。方法:取24例心脏病患者的右心耳组织(房颤12 例,为房颤组；窦性心律12 例，为窦律组)。（1）HE染色，观察房颤组与窦律组心肌纤维以及细胞核、细胞外基质的差异。（2）免疫组化染色，在普通显微镜下观察窦律组与房颤组心房Ⅰ型胶原并使用图像分析系统分析2组的胶原含量分数（collagen volume fraction, CVF），统计2组间Ⅰ型胶原含量分数（CVF-Ⅰ）的差异。（3）〖JP+1〗对CVF-I与左房直径进行Pearson相关分析。结果:(1)房颤组CVF-Ⅰ高于窦律组(CVF-I: 9.29 ±0.85 vs 6.90±1.47, P<0.01)；（2）房颤组心房大于窦律组（6.16±1.01 vs 4.47±0.99， P<0.01）；（3）心房大小与Ⅰ型胶原含量不存在相关性（r=0.33, P>0.05）。 结论:房颤患者的心房纤维化程度增加、左心房扩大，纤维化与左房扩大可能通过一定的途径，直接或间接参与了房颤的发病过程。     

白细胞介素-2预处理对缺氧/复氧心肌细胞收缩功能的影响

目的：观察白细胞介素-2（IL-2）预处理对缺氧/复氧过程中心肌细胞收缩功能的作用并探讨其作用机制。方法： 采用酶解法分离成年大鼠心室肌细胞缺氧/复氧模型，用视频跟踪计算机系统记录测定单个心室肌细胞收缩。心室肌细胞收缩参数包括最大收缩幅度（dL）、细胞最大收缩速度（+dL/dtmax）、细胞最大舒张速度（-dL/dtmax）和舒张末期细胞长度。结果： ①缺氧/复氧过程中，缺氧5、10、15和20 min时，心肌细胞dL、+dL/dtmax和-dL/dtmax明显降低。复氧5 min 时±dL/dtmax和dL有所恢复，但复氧10 min后±dL/dtmax、dL和舒张末期细胞长度又明显降低。②2×103 U/L IL-2对心室肌细胞收缩无明显作用。用此浓度IL-2预处理心室肌细胞15 min可明显改善缺氧/复氧引起的心室肌细胞收缩功能的减弱。③用选择性κ-阿片受体拮抗剂nor-BNI（10-8 mol/L）预处理后，IL-2对缺氧/复氧过程中心室肌细胞收缩的影响被减弱。④PKC抑制剂chelerythrine(3×10-6 mol/L) 可明显减弱IL-2的作用。⑤IL-2对缺氧/复氧过程中心室肌细胞收缩的影响可被线粒体ATP敏感性钾通道阻断剂5-HD（10-4 mol/L)明显抑制。结论： 2×103 U/L IL-2预处理可明显改善缺氧/复氧心室肌细胞的收缩功能。其作用是由κ-阿片受体介导的，IL-2作用的信号转导途径涉及PKC和线粒体ATP敏感性钾通道。     

成人心房肌细胞的急性分离和电生理学鉴定

目的：介绍一种适用于成人的心房肌细胞膜片钳研究的急性分离方法，并对所分离的细胞进行电生理学鉴定。 方法： 采用两步酶解与机械分离相结合的方法制备成年人心房肌细胞标本，应用倒置显微镜初步观察细胞形态、数目后，用全细胞膜片钳技术鉴定细胞的电生理学特性。 结果： 分离的细胞呈多种形态，其中有良好折光性、细胞膜完整、有清晰横纹的杆状细胞约占50%-60%，计算出11例独立实验分离出的此类细胞获得率为（57.2±3.1）%；具有正常的电生理学特性，能够诱发出人心房肌细胞上主要的Na+、K+通道混合电流以及心房肌细胞特有的超快速激活钾通道电流（IKur）。 结论： 实验数据表明该方法分离的细胞保持有其典型的通道特性，并证明其具有实用、快速和高效的特点，适用于人心房肌细胞的电生理学和电药理学研究，有良好的可行性。     

缝隙连接蛋白43通过调控L型钙电流参与心房肌细胞的电重塑

目的:观察缝隙连接蛋白43(Cx43)是否通过与L型钙通道共定位,调控L型钙电流,参与房颤(AF)的发病机制。方法:使用蛋白免疫印迹和实时荧光定量PCR检测AF和窦性心律患者心房组织中Cx43的蛋白和mRNA表达差异;用RNA干扰技术沉默心房肌细胞的Cx43表达,实时荧光定量PCR和全细胞膜片钳实验观察对L型钙通道mRNA表达和L型钙电流的影响;免疫共沉淀和激光共聚焦显微成像观察心房肌细胞中Cx43与L型钙通道是否存在共定位。结果:AF患者心房组织中的Cx43表达明显低于窦性心律患者;干扰Cx43表达可明显抑制L型钙电流和L型钙通道α1c亚基的mRNA表达;且心房肌细胞中Cx43与L型钙通道存在共定位。结论:心房肌细胞中的Cx43可通过与L型钙通道形成分子复合物,调控L型钙电流,参与心房肌细胞的电重塑。     

增龄犬左心房肌细胞动作电位和L型钙通道的变化

背景：增龄是心房颤动发生的独立危险因素,心房肌细胞电生理特性的变化是触发和维持心房颤动的重要因素。 目的：观察不同年龄犬左心房肌细胞动作电位和L型钙通道的改变。 方法：实验纳入7只成年犬和10只老年犬,用Ⅱ型胶原酶分离成年犬和老年犬的左心房肌细胞,用全细胞膜片钳方法记录成年犬和老年犬左心房肌细胞动作电位和L型钙通道电流;采用实时荧光定量PCR和Western blot检测左心房肌L型钙通道α1c亚基mRNA和蛋白的表达。 结果与结论：与成年犬相比,老年犬左心房肌细胞动作电位平台期的幅度明显降低(P < 0.05),动作电位时程明显延长(P < 0.05),而最大舒张电位和动作电位幅度在老年犬和成年犬间差异无显著性意义(P > 0.05);同时老年犬左心房肌细胞的L型钙通道电流密度较成年犬明显降低(P < 0.05),而L型钙通道电流动力学参数在成年犬和老年犬间差异无显著性意义(P > 0.05);此外,与成年犬相比,老年犬左心房肌L型钙通道α1c亚基mRNA和蛋白的表达明显降低(P < 0.05)。由此认为,左心房肌细胞电生理学特性存在增龄性改变。     

卡托普利对缺氧/复氧乳鼠心室肌细胞游离钙的影响及其离子通道机制

目的：观察卡托普利晚期预处理对缺氧/复氧乳鼠心室肌细胞游离钙的影响及其离子通道机制。方法:建立培养乳鼠心肌细胞缺氧/复氧损伤模型。设正常对照组、缺氧/复氧组、缺氧预适应组和卡托普利组。经Flou-3/AM负载染色后，采用流式细胞分析技术，测定细胞内钙离子浓度(［Ca²⁺］i)；利用膜片钳技术，观察L-型钙通道和钠钙交换电流的变化。结果:（1）缺氧/复氧时，［Ca²⁺］i和Na⁺/Ca²⁺交换电流高于正常对照组（P<0.01），L-型钙电流（I_Ca-L）峰值下降，I-V曲线上移，半数失活电压(V_0.5)减小，ICa-L失活曲线左移。（2）晚期预处理和卡托普利使缺氧/复氧时［Ca²⁺］i低于缺氧/复氧组（P<0.01）；I_Ca-L增加，I-V曲线下移，V_0.5增大及稳态失活曲线右移；Na⁺/Ca²⁺ 交换电流减少；但［Ca²⁺］i和Na⁺/Ca²⁺交换电流高于对照组（P<0.05）。（3）卡托普利组与缺氧预适应组比较上述指标均无显著差异 。结论：心肌细胞缺氧/复氧，通过Na⁺/Ca²⁺交换电流的异常增加可引起［Ca²⁺］i的异常升高及其钙超载；卡托普利通过轻度增加Na⁺/Ca²⁺交换电流及其［Ca²⁺］i而触发晚期预处理，抑制后续缺氧/复氧引起的Na⁺/Ca²⁺交换电流及其［Ca²⁺］i的异常增加。     

Ryanodine-, IP3- and NAADP-dependent calcium stores control acetylcholine release

Injections of inositol trisphosphate (IP3) or nicotinamide adenine dinucleotide phosphate (NAADP) into the presynaptic neurone of an identified cholinergic synapse in the buccal ganglion of Aplysia californica increased the amplitude of the inhibitory postsynaptic current evoked by a presynaptic action potential. This suggests that Ca2+ release from various Ca2+ stores can modulate acetylcholine (ACh) release. Specific blockade of the calcium-induced calcium release (CICR) mechanism with ryanodine, or of IP3-induced calcium release with heparin, abolished the effects of IP3, but not the effects of NAADP, suggesting the presence of an intracellular Ca2+ pool independent of those containing ryanodine receptors (RyR) or IP3 receptors. To reinforce electrophysiological observations, intracellular [Ca2+]i changes were measured using the fluorescent dye rhod-2. Injections of cyclic ADP-ribose (an activator of RyR), IP3 or NAADP into the presynaptic neurone induced transient increases in the free intracellular Ca2+ concentration. RyR- and IP3-induced increases were prevented by application of respective selective antagonists but not NAADP-induced increases. Our results show that RyR-dependent, IP3-dependent, and NAADP-dependent Ca2+ stores are present in the same presynaptic terminal but are differently involved in the regulation of the presynaptic Ca2+ concentration that triggers transmitter release.     

Voltage-sensitive calcium flux into bovine chromaffin cells occurs through dihydropyridine-sensitive and dihydropyridine- and omega-conotoxin-insensitive pathways

The fluorescent Ca2+ indicator FURA-2 was used to characterize the depolarization-related intracellular Ca2+ signalling process in bovine adrenal chromaffin cells. Depolarization with high K+ (10-65 mM) gave rise to a very rapid increase in intracellular free Ca2+ concentration, which subsequently decayed slowly towards a "plateau". The size of this initial increase varied sigmoidally with the calculated membrane potential, the relationship being described well by a Boltzmann distribution function for a transition between two states (transition potential, -23 mV). A dihydropyridine calcium channel agonist [(+)202-791, 1 microM] raised intracellular free Ca2+ concentration further in the presence of 30 mM K+, and it enhanced the initial intracellular Ca2+ response to depolarization. Voltage-sensitive calcium channels in chromaffin cells are believed to include the L-type. Several dihydropyridine calcium channel antagonists [(-)202-791, nifedipine, nitrendipine; 1-5 microM], known to be active on L-type channels, caused only modest inhibition of K+ -induced increase in intracellular free Ca2+ concentration: c. 50% (at 30 mM K+) and 25% (at 40-70 mM K+). In addition, omega-conotoxin GVIA (1-10 microM), a blocker of neuronal N- and L-type calcium channels, reduced the initial increase in intracellular free Ca2+ concentration only slightly at 55 mM K+. Further, the dihydropyridine-insensitive component of the intracellular Ca2+ signal was also insensitive to omega-conotoxin, which was otherwise quite active in a central nervous rat in vivo preparation Gd3+ (40 microM), a potent calcium antagonist in the chromaffin cell, blocked the intracellular Ca2+ response to depolarization. When added at different times after K+ stimulation, however, Gd3+ reduced intracellular free Ca2+ concentration to control levels along a slow time course of several minutes. Similar results were obtained when EGTA was added to reduce extracellular Ca2+ concentration to sub-nanomolar levels, in the presence of high K+. We conclude that bovine chromaffin cells are equipped with at least two different classes of voltage-dependent calcium channels, only one of which is likely to be the L-type channel. We also propose that depolarization, in addition to stimulating Ca2+ influx, may also lead to enhancement of Ca2+ release from an intracellular store.     

The non-excitable smooth muscle: Calcium signaling and phenotypic switching during vascular disease

Calcium (Ca(2+)) is a highly versatile second messenger that controls vascular smooth muscle cell (VSMC) contraction, proliferation, and migration. By means of Ca(2+) permeable channels, Ca(2+) pumps and channels conducting other ions such as potassium and chloride, VSMC keep intracellular Ca(2+) levels under tight control. In healthy quiescent contractile VSMC, two important components of the Ca(2+) signaling pathways that regulate VSMC contraction are the plasma membrane voltage-operated Ca(2+) channel of the high voltage-activated type (L-type) and the sarcoplasmic reticulum Ca(2+) release channel, Ryanodine Receptor (RyR). Injury to the vessel wall is accompanied by VSMC phenotype switch from a contractile quiescent to a proliferative motile phenotype (synthetic phenotype) and by alteration of many components of VSMC Ca(2+) signaling pathways. Specifically, this switch that culminates in a VSMC phenotype reminiscent of a non-excitable cell is characterized by loss of L-type channels expression and increased expression of the low voltage-activated (T-type) Ca(2+) channels and the canonical transient receptor potential (TRPC) channels. The expression levels of intracellular Ca(2+) release channels, pumps and Ca(2+)-activated proteins are also altered: the proliferative VSMC lose the RyR3 and the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase isoform 2a pump and reciprocally regulate isoforms of the ca(2+)/calmodulin-dependent protein kinase II. This review focuses on the changes in expression of Ca(2+) signaling proteins associated with VSMC proliferation both in vitro and in vivo. The physiological implications of the altered expression of these Ca(2+) signaling molecules, their contribution to VSMC dysfunction during vascular disease and their potential as targets for drug therapy will be discussed.     

The gating and conductance properties of Cav3.2 low-voltage-activated T-type calcium channels

Calcium channels are essential for excitation-contraction coupling and pacemaker potentials in cardiac muscle cells. Whereas L-type Ca(2+) channels have been extensively studied, T-type channels have been poorly characterized in cardiac myocytes. We describe here the functional properties of recombinant Ca(V)3.2 T-type Ca(2+) channels expressed in mammalian cell lines. The T-type Ca(2+) current showed a rapid activation and an inactivation phase in response to depolarization, and it displayed a window current over the voltage range from -60 to -40 mV in 1 to 10 mM external Ca(2+). Barium (Ba(2+)) and strontium (Sr(2+)) permeate the channel with similar activation kinetics. On the other hand, monovalent cations, Li(+) and Na(+), permeate the T-type Ca(2+) channel more easily than the L-type Ca(2+) channel. The permeability order of the Ca(V)3.2 T-type Ca(2+) channel among monovalent and divalent cations was determined as Ba(2+)>Mn(2+)>Ca(2+)>Sr(2+)>Li(+1)>Na(+) with the permeability order of 1.39:1.25:1.00:0.95:0.55:0.29. The ionic conductance sequence for cations relative to calcium was Sr(2+)>Ba(2+)>Ca(2+)>Li(+1)>Mn(2+)>Na(+) with the conductance ratio of 1.39:1.21:1.00:0.40:0.23:0.11. The permeation profile of manganese (Mn(2+)) is complex. Mn(2+) permeates the Ca(2+) channel with a permeability similar to Ca(2+) or Ba(2+), but with a much smaller current density, resulting in a much smaller conductance. The properties relating to progression and recovery from inactivation in the Ca(V)3.2 channel are substantially identical with either Ca(2+) or Ba(2+) as the charge carrier.     

Both 3,4-dihydroxyphenylalanine and dopamine releases are regulated by Ca2+-induced Ca2+ releasing system in rat striatum

To clarify the striatal Ca2+-dependent monoaminergic exocytosis mechanisms, this study determined the effects of the Ca2+-induced Ca2+ releasing system (CICR), containing inositol-trisphosphate-receptor (IP3R) and ryanodine-receptor (RyR), on striatal releases of dopamine and its precursor, 3,4-dihydroxyphenylalanine (DOPA), using microdialysis. The basal dopamine release is regulated by IP3R but not by RyR, whereas basal DOPA release does not require CICR. The K+-evoked releases of DOPA and dopamine were enhanced by IP3R agonist, whereas RyR agonist reduced it. Additionally, inhibition of dopamine release induced by RyR hyperactivation was prevented by inhibition of L-type voltage-sensitive Ca2+-channel activity. These present results suggest that CICR-associated regulation of striatal releases of DOPA and dopamine is restrictive during the resting stage, whereas CICRs play an important role as a reserve mechanism of exocytosis of striatal DOPA and dopamine during the hyperexcitable stage.     

心肌L型钙通道/电流及其在心肌肥大和心力衰竭时的变化

心肌细胞电活动的基础就是各种通道的离子流。有两类离子流左右心肌细胞的电活动 :一类是内向离子流 ,包括Ｉｎａ、Ｉｎａ-ｂ、Ｉｆ、Ｉｃａ-Ｌ、Ｉｃａ-Ｔ;另一类是外向离子流 ,包括Ｉｔｏ(Ｉｔｏ1 、Ｉｔｏ2 )、ＩＫ(ＩＫｒ、ＩＫｓ、Ｉｋｐ)、ＩＫ1 、ＩＫ -ＡＴＰ、ＩＫ -Ａｃｈ等。心肌细胞的钙通道 /电流属内向电流 ,可分为两大类 :(1 )Ｌ型Ｃａ2 通道 /电流(ＩＣａ-Ｌ) ,它在决定心肌细胞动作电位平台期的内向电流和启动心肌细胞兴奋 -收缩耦联都发挥极其重要的作用。 (2 )Ｔ型Ｃａ2 通道 /电流 (Ｉｃａ-Ｔ) ,它可能在心脏起搏细胞…