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

软体动物心脏受多种心脏兴奋剂的调节 比如神经肽FMRFamide和神经递质， 5-羟色胺(5HT)。当前项目，使用作为主要 自参比钙电极技术，研究机理 其中5-羟色胺从不同的细胞隔室动员钙到 增强心室肌的收缩能力。 内侧孤立肌束、骨小梁的治疗 微摩尔浓度为5-羟色胺的腹足动物脑室壁 导致一过性钙外流。这种外流很可能是 先前通过L型钙通道的钙内流 反映心脏肌膜的快速挤出机制 肌细胞。类似的效果在前面的 对FMRFamide作出反应的心脏制剂(Devlin，1997)。然而， 与5-羟色胺刺激的外排有显著差异。 和FMRFamide的。5-羟色胺诱导的外流通常是一种小的， 短暂的瞬变，而FMRFamide不仅导致更多 持续外流，但外流幅度较大。 来检验钙首先是通过 电压门控型L通道，异搏定(钙通道阻滞剂) 和BAY K 8644(通道激动剂)。维拉帕米和维拉帕米 BAY K 8644对自发性外排无影响。然而，维拉帕米 抑制5-羟色胺刺激的钙外流，而Bay K 8644 增强了外流。这些数据证实了先前的发现。 (Devlin，1997)发现无脊椎动物的肌肉对 哺乳动物的L型通道，这是进一步支持 钙通道药物的使用依赖机制。 使用无Na+、锂取代的生理盐水或苯扎米 研究Na/Ca交换器在钙外流中的作用。治疗 使用无钠离子、锂离子取代的生理盐水的小梁没有 对自发性钙外流的影响，但极大地抑制 5-羟色胺诱导的外排。苯扎米引起持续的钙内流， 与5-羟色胺同时治疗则略有增强。 环匹阿松酸抑制剂对小梁的治疗作用 肌浆网钙ATPase，完全消除了任何钙外流 5-羟色胺刺激。这一数据表明，5HT可能使用SR作为其 本区E-C耦合过程中的原生钙库 肌肉。德夫林，C.L.1997年。一种振动钙离子选择电极 测定神经肽FMRFamide诱导的大鼠心肌细胞内钙离子通量 腹足类脑室。公司。生物化学。物理。116A：93-100。

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.