钙通道阻滞剂在镇痛应用中的研究进展

感觉神经元细胞上存在电压依赖性钙通道,钙离子是神经元突触前膜兴奋和递质释放必要的偶联因子,阻断钙 的内流可影响感觉传导过程而产生抗伤害反应。本文就钙通道阻滞剂的中枢镇痛作用及对阿片类药物的影响予以综述。     

钙通道阻滞剂在镇痛应用中的研究进展

感觉神经元细胞上存在电压依赖性钙通道，钙离子是神经元突触前膜兴奋和递质释放必要的偶联因子，阻断钙的内流可影响感觉传导过程而产生抗伤害反应。本文就钙通道阻滞剂的中枢镇痛作用及对阿片类药物的影响予以综述。     

钙通道阻滞剂与瘢痕治疗

钙离子作为细胞内一种重要离子 ,直接参与细胞兴奋———收缩偶联过程和以三磷酸肌醇 (ＩＰ3 ) ,二酰甘油 (ＤＧ)为第二信使的信息传导过程 ,与许多的细胞事件如核膜崩解 ,染色质浓缩和细胞分裂有关。细胞内钙水平的调节通过以下途径实现 :钙离子通道 (受体调控和电压依赖性 ) ,钠钙交换 ,钙泵以及细胞内部的钙摄取与释放 (线粒体和肌浆网等 )。现有的钙通道阻滞剂都作用于电压依赖性和钙通道 ,能抑制细胞外液钙离子内流 ,使细胞内钙离子浓度降低而发挥生物学效应。应用钙通道阻滞剂治疗高血压虽已有 2 0余年 ,但 1992年Ｌｅｅ[1] 才首先报…     

休克、缺血性损伤与钙及钙通道阻滞剂

近年来的研究表明,休克、缺血性损伤时,细胞内钙离子环境的失调,造成细胞内钙离子超负荷,是导致细胞不可逆性损伤和死亡的重要因素,也是各种因素所引起的细胞坏死的最终共同途径。钙通道阻滞剂能阻断钙向细胞内流,维持细胞内钙离子环境稳定性,减轻细胞损伤和保护器官功能,已越来越受到重视。本文就钙离子与细胞损伤的关系及钙通道阻滞剂的保护作用作一综述。     

兰尼碱受体拮抗剂——丹曲洛林的细胞保护作用

作为第二信使，钙离子在多种细胞功能活动中均有重要作用。如果钙离子的细胞内稳态受到破坏，则可导致细胞毒性反应甚至细胞死亡。钙通道兰尼碱受体激活，可致细胞内钙库释放过多从而}I起细胞损伤。而缺血、缺氧、癫痫、创伤、麻醉及神经退变性疾病的动物模型和组织培养实验中皆可观察到钙离子内稳态异常。丹曲洛林属兰尼碱受体拮抗剂，最早用于治疗恶性高热。丹曲洛林可抑制细胞内主要钙库——内质网过多释放钙离子。丹曲洛林可能的抗损伤细胞保护作用已在不同的组织培养模型或动物疾病模型中得到广泛的研究，此类模型均涉及细胞内钙离子稳态破坏所介导的细胞毒效应。本文中我们综述了钙离子内稳态破坏在细胞死亡中的作用，丹曲洛林的药理学和药代动力学特点，丹曲洛林的细胞保护作用以及在众多应激和疾病模型中抑制细胞损伤的潜在应用价值。     

人类精子中电压依赖性钙通道的研究进展

钙离子作为生物信使广泛存在于组织细胞中,影响细胞的许多功能。目前有关生殖细胞中和钙离子密切相关的钙离子通道的研究报告逐渐增多,现将有关人类精子中的电压依赖性钙通道的研究进展综述如下。     

钙通道阻滞剂与胰腺疾病

钙通道阻滞剂与胰腺疾病曹天生综述史海安审校钙离子是细胞内包括细胞增生的各种生物反应的一种重要中介物质。钙通道阻滞剂是近年心血管药理学的重要进展之一，研究发现该类药物对急性胰腺炎（ＡＰ）和胰腺肿瘤有一定程度的治疗作用。一、钙通道阻带剂与急性胰腺炎目前，...     

钙通道阻滞药在脑复苏中的作用

心脏骤停的存活者中,常有永久性神经损害。1973年Hossman等系统研究了猫和猴脑缺氧时的生化变化,发现在60分钟的缺血缺氧后,高能代谢、酶功能和动作电位尚能恢复。这些证据有力表明了4～6分钟的脑缺血或缺氧并不造成神经元的即刻死亡。复苏后缺血缺氧性脑死亡可能有其他机制参与。过去十年的研究发现许多器官和组织细胞的病理过程与钙离子参与有关。近年来实验资料表明,在休克、败血症、创伤和缺氧后出现的多种病理过程中,钙离子可能充当了一种触发剂。脑缺血缺氧后神经细胞内钙离子增多所致的代谢异常、游离脂肪酸释放、氧自由基形成以及无血流再通现象均可引起神经损害,而钙通道阻滞药则可改善这些病理改变。     

P物质对大鼠心肌细胞L-型钙通道电流的影响

P物质(SP)是一种广泛分布于外周及中枢神经系统的肽类物质.心肌缺血可刺激心脏感觉传入纤维,导致心肌化学性传人通路激活,引起传人神经末梢释放SP[1,2].心肌细胞L-型钙通道电流(ICa-L)是维持动作电位复极化平台期的重要内向电流,可通过激活肌浆网释放Ca2+,导致细胞内钙离子浓度升高.钙稳态失衡可引发严重的心力衰竭或钙超载,而后者是导致细胞凋亡的机制之一[3].本研究拟探讨SP对大鼠心肌细胞ICa-L的影响,为探讨SP在急性心肌缺血中的作用提供参考.     

异丙酚对大鼠心肌细胞钙离子移动及钙通道电流的影响

目的 观察异丙酚对心肌细胞钙离子移动和Ｌ－型钙通道电流（Ｉｃａｌ）的影响。方法 急性分离的大鼠单个心室肌细胞，采用Ｆｌｕｏ－３ＡＭ钙荧光指示剂和膜片钳技术，观察５０μｍｏｌ．Ｌ＾－１或２５０μｍｏｌ．Ｌ＾－１异丙酚对高浓度ＫＣ１或咖啡因所诱发细胞内钙离子浓度的变化，以及对Ｌ－型钙通道电流的影响。结果 ５０μｍｏｌ．Ｌ＾－１或２５０μｍｏｌ．Ｌ＾－１异丙酚明显减弱ＫＣｌ所诱发细胞内钙离子的增加，浓度     

hCG/ATP-induced Leydig cell calcium channel reaction at different extracellular calcium ion concentration

Objective: To study the calcium channel reaction of human Leydig cells induced by hCG/ATP at different extracellular calcium ion concentrations. Methods: The Leydig cell calcium ion concentration was examined with laser confocal microscope, when the cells were stimulated with hCG/ATP at different extracellular calcium contrations. Results: With calcium-containing extracellular fluid, the Leydig cells were sensitive to hCG stimulation and when the extracellular fluid was calcium-free, the Leydig cells did not respond to the stimulation. However, the Leydig cells did respond to ATP stimulation no matter the extracellular fluid contained calcium or not. Conclusion: In human Leydig cells, there are calcium channels sensitive to hCG and ATP. The extracellular calcium ion concentration plays an important role in the regulation of Leydig cell metabolism by hCG/ATP.     

Calcium ions are abnormally distributed in the skin of haemodialysis patients with uraemic pruritus.

BACKGROUND: Although a close relationship between uraemic pruritus and serum calcium levels has been demonstrated for some time, the degree of pruritus was not always correlated with calcium concentrations. In the present study, we assessed calcium ion distribution in the skin of chronic haemodialysis patients with and without pruritus. METHODS: We excluded patients with concomitant psoriasis or atopic dermatitis or with a previous history of allergy, those who had an arteriovenous fistula created prior to induction of haemodialysis, and patients with only mild pruritus. From the enrolled 22 haemodialysis patients, we obtained forearm skin samples during arteriovenous fistula surgery. These patients were divided into two groups based their grade of pruritus. The pruritus group included patients with moderate to severe grades of pruritus (n = 11, age 64 +/-13 years) and the non-pruritus group consisted of patients without pruritus (n = 11, age 59 +/-13 years). We compared the distribution of calcium ions in the epidermis between the two groups using the ion-capture method (oxalate-pyroantimonate-osmium technique). In addition, we examined and compared the groups for thicknesses of the basal, spinous and granular layers, as well as of the stratum corneum using an electron microscope. RESULTS: The pruritus group had significantly higher calcium ion deposition in the extracellular fluid and cytoplasm of basal cells, and in the extracellular fluid, nuclei and cytoplasm of spinous cells compared with the non-pruritus group. In contrast, calcium ion depositions were similar between the two groups in the dermis/basal layer interface, the nucleus of basal cells, the nucleus and cytoplasm of granular cells, exterior of granular cells, the granular cells/stratum corneum interface, and in the interior and exterior of corneocytes. Although the stratum corneum was significantly thicker in the pruritus group than in the non-pruritus group, there were no differences in basal cell, spinal cell or granular cell layer thicknesses. CONCLUSION: In chronic haemodialysis patients with pruritis, the calcium ion concentration in the deepest layer of the epidermis was increased, which indicated a disrupted calcium ion gradient in the skin. These findings point to a role for increased skin calcium ion concentrations in the development and/or maintenance of uraemic pruritus. However, more extensive studies in larger patient cohorts will be necessary to confirm this hypothesis.     

Cytosolic calcium concentration in bovine growth plate chondrocytes

The cytosolic free calcium ion concentration for mammalian cell systems is believed to be maintained within a narrow range compatible with cellular homeostasis. Growth plate chondrocytes have been shown to accumulate large quantities of calcium within their mitochondria, but the cytosolic free calcium concentration has not been determined. This study measures the cytosolic free ionic calcium concentration in growth plate chondrocytes using two variations of the Quin II fluorescence technique. The results indicate that in isolated growth plate chondrocytes, the cytosolic free ionic calcium concentration is similar to other nonmineralizing mammalian cell types (106–137 nM).     

A proposed cellular mechanism for calcium transport in the intestinal epithelial cell

Summary Intracellular transport of calcium from the apical to the basal-lateral region of the intestinal epithelial cell was invetigated in duodenum from normal fed, fasted, and calcium-loaded rats. The process was followed with time using electron microscopy with potassium pyroantimonate to precipitate calcium. The observations made were subjected to morphometric analysis. The specificity of the method was demonstrated in the villus cell by resistance to micro-incineration and by absence of deposits following exposure to EGTA. Using this method calcium was seen in cells from calcium-fed rats at the microvillus border, in the Golgi zone, and within the internal compartments of the mitochondria. In cells from fasted rats calcium was not seen. Mitochondria were found largely at the apex of the cell and were free of detectable calcium. By 5 min, in the cells of fasted rats given a calcium load, the calcium had reached the Golgi apparatus and the inner mitochondrial compartment. After 15 min mitochondria were heavily loaded with calcium and had moved to the basal region of the cell. These observations suggest that mitochondria play an important role in absorption of calcium and appear to transport this ion from the apex to the basal region of the cell where entry into the capillaries takes place.     

钙离子超载对低温保存人肝细胞的损伤作用的研究

目的：研究分离培养的成人肝细胞在低温保存状态下（0-4℃）的钙离子代谢特点和钙离子超载的损伤作用机制。方法：胶原酶消化法制备分离的成人肝细胞,钙离子荧光探针Flou-3标记,流式细胞仪检测。结果：低温保存下,细胞内游离钙迅速升高,逐渐达到稳态水平,随细胞内钙离子的升高,细胞的存活率也逐渐下降,但在含0.5mmol/L CaCl2的保存液组,保存效果明显好于其它两组;在含1.5mmol/L CaCl2的保存液组,继发的钙离子超载峰值出现早,而且要高于原发的钙超载峰。结论：低温保存可以引起成人肝细胞的钙超载,细胞外钙是细胞钙超载的主要来源,继发超载是缺血再灌注损伤的主要原因。     

Mechanism of amphotericin B stimulation of net calcium efflux from neonatal mouse calvariae

Amphotericin B is a polyene antifungal agent that binds to membrane sterols, creating aqueous pores that permit ion fluxes sufficient to cause cell lysis. It has also been shown to alter ion transport in mammalian cells, including proton secretion from renal tubular cells. The latter effect can lead to distal renal tubular acidosis in patients treated for systemic fungal infections. Based on the understanding that osteoclast-mediated bone resorption is dependent on proton secretion, we examined the effect of amphotericin B on calcium efflux from neonatal mouse calvariae in organ culture. Amphotericin B (5 micrograms/ml) stimulated net calcium efflux from calvariae within 24 h to a level almost as great as that produced by a maximally effective concentration of parathyroid hormone. The stimulated calcium efflux was completely inhibited by both 10 ng/ml salmon calcitonin, a physiologic inhibitor of osteoclast activity, and 4 x 10(-4) M acetazolamide, a specific inhibitor of carbonic anhydrase, the enzyme necessary for substantial proton generation by osteoclasts. These results indicate a direct effect of amphotericin B on bone in vitro to stimulate osteoclast-mediated calcium efflux.     

Stimulation of bone union by externally applied radio-frequency energy

Pulsed radio-frequency electrical energy has been used for many years in the treatment of various soft tissue lesions, and this paper describes its use in stimulating repair in delayed and non-union, with a success rate in 16 cases equal to that of the other electrical stimulation techniques. The equipment is described and a theory proposed that the cell membrane has a diode effect in allowing the absorption of electrical charge, which, by its influence on the calcium ion, stimulates the cell into activity.     

Potential contribution of optional urease-positive bacteria to idiopathic urinary calcium stone formation

We investigated the effects of weak to moderate urease hydrolysis by optional urease-positive microorganisms in an artificial urine model enriched with calcium phosphate and calcium oxalate in respect of calcium stone formation. The incubation experiments were performed using a discontinuously running fermenter device to simulate the urinary system. The kinetics of cell division rates, pH and ammonium ion production were measured and correlated to crystallite appearance in the incubation medium. Qualitative analyses of the sediments revealed apatite. Investigations using light microscopy and scanning electron microscopy (SEM) confirmed the matrix effect of bacterial glycoproteins. It was shown that initiation of calcium oxalate stone formation is in all probability equally determined by matrix effects and by heteronuclear crystailization if the urinary tract is infected by optional urease-positive bacteria. When urinary inorganic phosphate is present, calcium phosphate nidi are always initially formed, and may subsequently be coated by calcium oxalate.     

The effect of ions at the surface of calcium oxalate monohydrate crystals on cell-crystal interactions

Magnesium is an abundant ion in biologic systems, including renal tubular fluid; however, the precise role of magnesium during the interaction of calcium oxalate crystals with cells has not been previously defined. In addition, the respective roles of calcium and hydrogen ions during the cell-crystal bonding interaction remain poorly defined. Here we report an atomic level three-dimensional study of a single crystal of calcium oxalate monohydrate (COM; whewellite) which was bathed in a solution of magnesium hexahydrate for 1 year. Magnesium was not incorporated into the structure of whewellite to any significant degree. Instead, COM accepted magnesium primarily as an adsorbate in a binding configuration which, as a surface phenomenon, is controlled by localized charge effects. The effect of magnesium and calcium on the efficiency of calcium oxalate crystal binding to renal cells was also investigated. When present in supraphysiologic concentrations (greater than 0.1 M), magnesium progressively inhibited adhesion of pre-formed COM crystals to cultured renal cells. Therefore, even though magnesium does not incorporate into the crystal structure of calcium oxalate, magnesium can exert important surface effects and change the interaction of pre-formed COM with molecules anchored on the cell surface. Similarly, binding was nearly blocked when the exogenous calcium concentration was > or =0.1 M (supraphysiologic range), although in lower concentrations (within the physiologic range) exogenous calcium promoted crystal adhesion. Finally, the ambient hydrogen ion concentration also influenced calcium oxalate crystal interactions with renal cells, with maximal binding occurring at a pH of 4. Therefore, hypercalciuria and/or an acidic urine could each promote renal stone formation via increased crystal adhesion to renal cells, a previously under-appreciated potential mechanism.     

How is plasma calcium concentration held constant?

Summary: Extracellular or plasma calcium ion concentration is held constant at 5 mg/dL through the actions of parathyroid hormone (PTH), vitamin D and calcitonin, on their target organs, kidney and bone. the thresholds of renal tubular calcium reabsorption and bone resorption and formation are both set at 5 mg/dL. the set-point of PTH secretion is also set at 5 mg/dL plasma calcium ion. Thus, the sensing system (parathyroid cell) and the effectors, kidney and bone, are all set to maintain plasma calcium at 5 mg/dL, and such setpoint in each organ may be determined by the membrane bound calcium sensor proteins. the effectiveness of this system depends upon the presence of bone remodelling, which allows a swift move of plasma calcium from and to bone in response to PTH and calcitonin, respectively. In this regard, directing haematopoiesis to bone marrow which provides bone resorbing osteoclasts is critical. It is likely that this shift of haematopoiesis occurs through evolution at the transition from the aquatic to the terrestrial life and this event is directed by expression of 'homing molecule' in bone marrow stromal cells. This brief review provides a factual and conceptual framework of the current understanding how plasms calcium is held constant at 5 mg/dL.