Mészàros J, Pappano A J
Department of Pharmacology, University of Connecticut Health Center, Farmington 06032.
Am J Physiol. 1990 Apr;258(4 Pt 2):H931-8. doi: 10.1152/ajpheart.1990.258.4.H931.
In isolated guinea pig ventricular myocytes, L-palmitoylcarnitine (L-PC) produced concentration- and time-dependent changes of resting potential (RP) and action potential duration at 50% repolarization (APD50). At 10(-8) to 10(-6) M, L-PC increased APD50 without changing RP. At 10(-5) M, the amphiphile initially increased (0-10 min) and eventually decreased (greater than 10 min) APD50; the membrane depolarized when APD50 decreased. Additionally, transient depolarizations (TDs) were consistently induced in 10(-5) M L-PC within 10 min, and TD amplitude progressively increased with continued exposure to L-PC. The TDs induced in L-PC were augmented by membrane depolarization, elevated extracellular Ca2+ concentration ([Ca2+]o), and increased number of stimuli. Elevated [Ca2+]o or neuraminidase treatment also allowed TDs. In neuraminidase, the changes of RP, APD50, and TD amplitude were qualitatively similar to those seen with L-PC. These results are consistent with the hypothesis that 10(-5) M L-PC causes intracellular Ca2+ overload. The blockade of L-PC and neuraminidase-induced TDs by ryanodine is consistent with the intracellular Ca2+ overload hypothesis.
在分离的豚鼠心室肌细胞中，L-棕榈酰肉碱（L-PC）引起静息电位（RP）以及复极化50%时动作电位时程（APD50）的浓度和时间依赖性变化。在10^(-8)至10^(-6) M时，L-PC增加APD50而不改变RP。在10^(-5) M时，这种两亲分子最初增加（0 - 10分钟），最终降低（大于10分钟）APD50；当APD50降低时膜发生去极化。此外，在10^(-5) M L-PC中10分钟内持续诱导出瞬时去极化（TDs），并且TD幅度随着持续暴露于L-PC而逐渐增加。L-PC诱导的TDs因膜去极化、细胞外Ca2+浓度（[Ca2+]o）升高以及刺激次数增加而增强。升高的[Ca2+]o或神经氨酸酶处理也能引发TDs。在神经氨酸酶作用下，RP、APD50和TD幅度的变化在性质上与L-PC作用时相似。这些结果与10^(-5) M L-PC导致细胞内Ca2+超载的假说一致。ryanodine对L-PC和神经氨酸酶诱导的TDs的阻断与细胞内Ca2+超载假说相符。
