EFFECT OF ALPHA-ADRENERGIC STIMULATION ON ISOLATED VENTRICULAR MYOCYTES

α-肾上腺素刺激对离体心室肌细胞的影响

• 批准号: 3813644
• 负责人: M C CAPOGROSSI
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3813644
• 关键词: alpha adrenergic agent; calcium metabolism; chemical stimulation; drug interactions; electrostimulus; heart cell; heart contraction; heart pharmacology; heart rhythm; heart ventricle; laboratory rat; membrane permeability; muscle relaxants; muscle stimulant; phenylephrine; prazosin; propranolol; sarcoplasmic reticulum; single cell analysis

The effect of alpha1-adrenergic stimulation on the inotropy of the myocardium is still controversial. A positive inotropic effect has been well documented and it is often preceded by a short lived decrease in contractility. Additionally a persistent negative inotropic effect of alpha, stimulation has also been described in multicellular cardiac preparations. The purpose of this study was to characterize the effect of alpha1 stimulation on the cytosolic Ca transient and on the contractile properties of single ventricular myocytes under condition leading either to an enhancement or a decrease in twitch amplitude. Isolated rat ventricular myocytes, pretreated with propranolol were used to investigate the effect of alpha1-adrenergic stimulation with phenylephrine on contractility, cytosolic Ca homeostasis and on the frequency of spontaneous contractile waves (CW), which represent the mechanical expression of spontaneous calcium release from the sarcoplasmic reticulum (SR). a) In 1 mM bathing [Ca2=] (Ca), during field stimulation at 0.2 Hz, alpha had a positive inotropic effect which was reversibly abolished by prazosin and appeared related to an increased myofilament responsiveness to calcium in addition to some enhancement in the amplitude of the cytosolic Ca transient associated with the twitch. b) During stimulation at 0.2 Hz, in 5 mM Cao, CW appeared in some of the diastolic intervals. Phenylephrine abolished them and decreased twitch amplitude. In similar experiments with myocytes loaded with the Ca probe Indo-1 AM the negative effect of alpha1 on TA was associated with a decrease in the amplitude of the cytosolic Ca transient. c) In the absence of stimulation, in 5 mM Cao, alpha1 significantly and reversibly reduced cytosolic and CW frequency. This effect could be prevented by the alpha1 blocker prazosin. No effect of phenylephrine on cytosolic Ca was observed at rest in 1 mM Cao. These findings are consistent with the view that the effect of alpha1-adrenergic stimulation of cardiac cells can vary in relation to intracellular Ca.

α_1肾上腺素能刺激对心肌收缩力的影响 心肌仍然是有争议的。 正性肌力作用已被证实 有据可查，在此之前， 收缩性 此外， 在多细胞心脏中也描述了α刺激， 准备工作。 本研究的目的是描述 α 1刺激对细胞质Ca瞬变和收缩性 单个心室肌细胞在导致以下任一情况下的特性 抽搐幅度的增强或减小。 大鼠心室 用普萘洛尔预处理的心肌细胞，观察其对心肌细胞增殖的影响。 用去氧肾上腺素刺激α 1肾上腺素能对收缩力的影响， 细胞质Ca稳态和自发收缩频率 波（CW），它代表了自发的机械表达 肌浆网（SR）释放钙。 a）在ImM浴中 [Ca2=]（Ca），在0.2 Hz的场刺激期间，α具有阳性 哌唑嗪可逆地消除了变力作用， 与肌丝对钙的反应性增加有关 胞质钙瞬变幅度的一些增强 与抽搐有关 B）在0.2 Hz刺激期间，在5 mM CaO中， CW出现在部分舒张间期。 苯巴比妥消除 他们和减少抽搐幅度。 在类似的肌细胞实验中 用Ca探针Indo-1 AM负载，α 1对TA的负作用被证实为 与胞质Ca瞬变幅度的降低相关。 c）在不存在刺激的情况下，在5 mM Cao中，α 1显著地和 可逆性降低胞质和CW频率。 这种作用可 被α 1受体阻滞剂哌唑嗪所阻止 去氧肾上腺素对 在1 mMCaO中观察到静止时的胞质Ca。这些发现 与α 1-肾上腺素能刺激的作用 心肌细胞的钙离子浓度与细胞内钙离子浓度有关。