脱氧胆酸钠对豚鼠心房机械和电活动及超微结构的影响。

Effects of sodium deoxycholate on the mechanical and electrical activities and ultrastructure of guinea pig atria.

作者信息

Tripathi O, Ray M, Bajpai V K, Bhatnagar A, Kumar R, Singh Y K, Singh C, Shipstone A C, Dhawan B N

机构信息

Department of Pharmacology, Central Drug Research Institute, Lucknow, India.

出版信息

Biomed Biochim Acta. 1988;47(9):901-14.

PMID:3248126

Abstract

The mechanism of cardio-inhibitory effects of sodium deoxycholate (DOC) was investigated by studying its effects on the contractility, action potentials (APs) and ultrastructure of guinea pig atrial preparations. DOC (10(-7)-10(-4) M) caused reversible negative ino- (NIE) and chrono-tropy in spontaneously beating (SBA) and NIE in electrically driven left (EDA) atria. At higher doses (greater than or equal to 1.10(-3) M) DOC caused irreversible inhibition of contractions. Atropine (10(-7)-10(-4) M) failed to inhibit both the reversible and irreversible effects of DOC. The NIE due to lower doses of DOC (less than or equal to 1.10(-4) M) was inhibited by higher [Ca2+]0, isoprenaline (10(-6)-10(-4) M), and noradrenaline (10(-6)-10(-5) M), which did not alter the dose of DOC required for the irreversible and complete NIE. In lower doses (10(-7)-10(-4) M) DOC caused a reversible inhibition of the AP durations at -20 and -40 mV (APD20 and APD40, respectively), but increased the AP duration at 90% repolarisation (APD90). At higher doses (greater than 5.10(-4) M) it caused an irreversible membrane depolarization, reduction in APD20 and APD40, and complete cessation of electrical activity. The ultrastructural changes in atria treated with 1.10(-4) M DOC were characterized by poorly delineated glycocalyx and at greater than 1.10(-3) M by disruption of sarcolemma and sarcoplasmic reticulum and swelling disruption of mitochondria. Taken together these observations show that DOC caused reversible and irreversible inhibition of atrial contractions at low (10(-7)-10(-4) M) and high (greater than 5.10(-4) M) concentrations, respectively, by different mechanisms. The former effect is due to inhibition of Ca2+ channel activity and the latter due to its detergent property causing removal of subcellular components.

摘要

通过研究脱氧胆酸钠（DOC）对豚鼠心房肌收缩性、动作电位（AP）和超微结构的影响，探讨其心脏抑制作用机制。DOC（10⁻⁷ - 10⁻⁴M）可使自发搏动心房（SBA）产生可逆性负性变力（NIE）和变时性作用，并使电驱动左心房（EDA）产生NIE。高剂量（≥1.10⁻³M）DOC可导致收缩的不可逆抑制。阿托品（10⁻⁷ - 10⁻⁴M）不能抑制DOC的可逆和不可逆作用。低剂量（≤1.10⁻⁴M）DOC引起的NIE可被高[Ca²⁺]₀、异丙肾上腺素（10⁻⁶ - 10⁻⁴M）和去甲肾上腺素（10⁻⁶ - 10⁻⁵M）抑制，这些物质不会改变产生不可逆和完全NIE所需的DOC剂量。低剂量（10⁻⁷ - 10⁻⁴M）DOC可使-20和-40mV处的动作电位时程（分别为APD20和APD40）产生可逆性抑制，但使90%复极化时的动作电位时程（APD90）延长。高剂量（＞5.10⁻⁴M）时，它可导致不可逆的膜去极化、APD20和APD40缩短以及电活动完全停止。用1.10⁻⁴M DOC处理的心房超微结构变化表现为糖萼界限不清，而在＞1.10⁻³M时表现为肌膜和肌浆网破坏以及线粒体肿胀破裂。综上所述，这些观察结果表明，DOC分别通过不同机制在低浓度（10⁻⁷ - 10⁻⁴M）和高浓度（＞5.10⁻⁴M）时引起心房收缩的可逆和不可逆抑制。前者作用是由于抑制Ca²⁺通道活性，后者是由于其去污剂特性导致亚细胞成分去除。