頁籤選單縮合
題 名 | Effects of the SR Ca[fec7] Pump Inhibitor Thapsigargin on Triggered Activity in Human and Hamster Myocardium |
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作 者 | Lin,Cheng-i; Shen,Yu-fun; Chen,Yao-chang; | 書刊名 | 醫學工程 |
卷 期 | 10:3 1998.06[民87.06] |
頁 次 | 頁8-12 |
分類號 | 418.1 |
關鍵詞 | Sarcoplasmic reticulum; Ca-pump; Cardiac tissues; Action potential; Contraction; Whole-cell voltage-clamp; Ionic currents; |
語 文 | 英文(English) |
英文摘要 | In the present study, we determined the effects of thupsigargin (TG), an inhibitor of the SR Ca�� pump, on the steady-state and the post-rest activity of human atrial and Syrian hamster veniricular muscles under condition of various inotropic interventions. Transmembrane action potentials (APs) of the multicellular preparations were recorded by conventional microelectrode techniques and contractile force by a transducer. L-type Ca currents (Ical), transient outward. K currents (1to) and arrhythmogenic transient inward currents (Iu) were also recorded with whole-cell voltage-clamp techniques in ventricular myocytes isolated enzymatically. Results show that TG (I-1O μM) did not significantly change the AP and force m preparations showing fast response Aps. In diseased human atrial fibers generated slow response AP in the presence of isoprolerenol. TG decreased the diastolic slope, suppressed, triggered activities and converted stow response APs lo fast response Aps. In hamster ventricular preparations driven in physiological salt solution, TG also did not change the post-rest (20 s) potentialion of twitch force. Combination of high-[Ca]o (5.4-8.1 mM) and low-[K]o (1 mM) could induce the delayed afterdepolarizations (DADs) and aftercontraclions (ACs): indications of a presence of intracellular Ca�� overload. After a resting period of 5-40s, the amplitude of DADs and ACs increased progressively and often triggered APs and contractions occurred within 1 min. TG (3 μM) inhibited the DADs and ACs and could abolish the triggered APs developed after rest. In veniricular myocytes superfused in K��- and Na��-free Tris solution in the presence of CsCl, TG (1-3 μM) inhibited reversibly the Icai. TG also inhibited the 1u generated in high- [Ca]o and low-[K]o solution in a concentration-dependent manner. However, TG did not change the magnitude of the Ito. Thus the depressant effects of TG on post- rest potentiation of triggered activity appear to be related to the inhibitory actions of TG on Ical and Iti. The above findings indicate that TG exerts antiarrhythmic effects in Ca�� -overloaded human and hamster cardiac muscles mainly through inhibitory actions on transmembrane cation influxes. |
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