MECH WHICH 5HT MOBILIZES CALCIUM TO ENHANCE CONTRACTILITY OF VENTRICULAR MUSCLE

5HT 调动钙以增强心室肌收缩力的机械装置

• 批准号: 6414928
• 负责人: C L DEVLIN
• 金额: $ 21.13万
• 依托单位: MARINE BIOLOGICAL LABORATORY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-01 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6414928
• 关键词: animal tissue; biomedical resource; cardiovascular system; human tissue; musculoskeletal system

Molluscan hearts are modulated by numerous cardioexcitatory agents such as the neuropeptide FMRFamide and neurotransmitter, 5-hydroxytryptamine (5HT). The current project, using as the primary technique self-referencing calcium electrodes, studied mechanisms by which 5HT mobilizes calcium from various cellular compartments to enhance the contractility of ventricular muscle. Treatment of isolated muscle bundles, trabeculae, from the inner wall of the gastropod ventricle with micromolar concentrations of 5HT caused transient calcium efflux. This efflux was probably the result of a previous influx of calcium through L-type calcium channels and reflects rapid extrusion mechanisms by the sarcolemma of the cardiac myocytes. A similar effect has been previously described in the cardiac preparation in response to FMRFamide (Devlin, 1997). However, there are pronounced differences between the efflux stimulated by 5HT and that of FMRFamide. 5HT-induced efflux was typically a small, short-lived transient, whereas FMRFamide caused not only a more sustained efflux but it was of larger magnitude. To test the hypothesis that calcium was first entering through voltage-gated L-type channels, verapamil (a calcium channel blocker) and Bay K 8644 (a channel agonist) were tested. Neither verapamil nor Bay K 8644 had any effect on spontaneous efflux. Verapamil however inhibited calcium efflux stimulated by 5HT, whereas Bay K 8644 potentiated the efflux. These data corroborate earlier findings (Devlin, 1997) that found invertebrate muscle to be sensitive to mammalian L-type channel, and is further evidence in support of a use-dependent mechanism by calcium channel drugs. A Na+-free, lithium-substituted saline, or benzamil, were used to study the role of the Na/Ca exchanger in calcium efflux. Treatment of the trabeculae with a Na+-free, lithium-substituted saline had no effect on spontaneous calcium efflux, but greatly inhibited 5HT-induced efflux. Benzamil caused a sustained calcium influx that was slightly potentiated by simultaneous treatment with 5HT. Treatment of the trabeculae with cyclopiazonic acid, an inhibitor of the SR calcium ATPase, completely eliminated any calcium efflux stimulated by 5HT. This data suggests that 5HT may use the SR as its' primary calcium reservoir during the process of E-C coupling in this muscle. Devlin, C.L. 1997. A vibrating Ca2+-selective electrode measures Ca2+ flux induced by the neuro-peptide FMRFamide in a gastropod ventricle. Comp. Biochem. Physiol. 116A: 93-100.

软体动物的心脏受到许多心脏兴奋剂的调节 如神经肽FMRFamide和神经递质， 5-羟色胺（5 HT）。 当前项目，使用 技术自参考钙电极，研究机制， 5-羟色胺从不同的细胞室中动员钙， 增强心室肌的收缩力。 从内部治疗孤立的肌束、小梁 具有微摩尔浓度的5 HT的腹足动物心室壁 引起了短暂的钙外流 这种外流可能是 先前通过L型钙通道的钙流入， 反映了心肌肌膜的快速挤出机制 肌细胞 类似的效果已经在前面的 对FMRFamide的心脏准备（Devlin，1997）。 然而，在这方面， 5-HT刺激的外排有明显差异， 和FMRFamide的那些。 5 HT诱导的外排通常是小的， 短暂的短暂，而FMRFamide不仅引起更多的 持续流出，但数量更大。 为了验证钙首先通过 电压门控L型通道，维拉帕米（钙通道阻滞剂） 和Bay K 8644（一种通道激动剂）。 维拉帕米和 Bay K 8644对自发外排有任何影响。 但是维拉帕米 Bay K 8644抑制5 HT刺激的钙外流，而Bay K 8644抑制5 HT刺激的钙外流。 增强了外排 这些数据证实了早先的发现 （Devlin，1997）发现无脊椎动物的肌肉对 哺乳动物的L型通道，并进一步证明了 钙通道药物的使用依赖性机制。 使用无Na+、锂取代的盐水或苯扎明， 研究Na/Ca交换体在钙外流中的作用。 治疗 不含Na+的锂替代盐水中的骨小梁没有 对自发性钙外流有影响，但受到极大抑制 5 HT诱导的外排。 苯扎米尔引起了持续的钙内流， 与5-HT同时处理可略微增强。 用抑制剂环匹阿尼酸治疗小梁 的SR钙ATP酶，完全消除任何钙外流 5 HT刺激。 这一数据表明，5 HT可能使用SR作为其“ 在E-C偶联过程中， 肌肉. Devlin，C.L. 1997. 振动式钙离子选择电极 测量由神经肽FMRFamide诱导的Ca 2+通量， 腹足动物心室。 Comp. Biochem. Physiol. 116 A：93-100.