Schouten V J, ter Keurs H E
Laboratory for Physiology, Free University, Amsterdam, The Netherlands.
J Mol Cell Cardiol. 1991 Sep;23(9):1039-50. doi: 10.1016/0022-2828(91)91639-9.
The inward Ca2+ current, ica, increases with the frequency of stimulation in single ventricular myocytes, but the presence and possible role of this phenomenon in intact heart muscle of mammals has not been studied. The present study addresses the question whether changes in ica play a role in the force-frequency relationship in thin ventricular trabeculae from rat heart. The duration of the action potential at 50% repolarization, APD50, is related to the strength and duration of ica (Mitchell et al., 1984b; Schouten, 1986). APD50 increased with the frequency of stimulation. Peak force of contraction, F, was minimal at 0.1-0.3 Hz and increased at both higher and lower frequencies, suggesting two mechanisms with opposite frequency-dependence. The increase at low frequencies was abolished by drugs that inhibit Ca2+ uptake by the sarcoplasmic reticulum (caffeine, theophylline), but not by Ca2+ antagonists that block ica (nifedipine, Mn2+). This is consistent with the hypothesis that a small net influx of Ca2+ across the sarcolemma during long diastoles was responsible for loading of the reticulum and enhancement of F at low frequencies. The increase of F and APD50 at high frequencies was abolished by Ca2+ antagonists but not by caffeine and theophylline. From this result it is concluded, that frequency-induced enhancement of ica occurs in intact heart muscle and contributes to the increase in F.
内向Ca2+电流（ica）在单个心室肌细胞中随刺激频率增加而增大，但该现象在哺乳动物完整心肌中的存在及其可能作用尚未得到研究。本研究探讨ica的变化是否在大鼠心脏薄心室肌小梁的力-频率关系中起作用。动作电位复极化50%时的时程（APD50）与ica的强度和时程相关（Mitchell等人，1984b；Schouten，1986）。APD50随刺激频率增加。收缩峰值力（F）在0.1 - 0.3 Hz时最小，在更高和更低频率时均增加，提示存在两种频率依赖性相反的机制。低频时的增加被抑制肌浆网摄取Ca2+的药物（咖啡因、茶碱）消除，但不被阻断ica的Ca2+拮抗剂（硝苯地平、Mn2+）消除。这与以下假设一致：在长舒张期期间少量Ca2+经肌膜净内流负责肌浆网的负荷及低频时F的增强。高频时F和APD50的增加被Ca2+拮抗剂消除，但不被咖啡因和茶碱消除。根据这一结果得出结论，在完整心肌中发生频率诱导的ica增强，且其有助于F的增加。
