Shen J B, Pappano A J
Department of Pharmacology, University of Connecticut Health Center, Farmington 06032.
Am J Physiol. 1995 Mar;268(3 Pt 2):H1027-36. doi: 10.1152/ajpheart.1995.268.3.H1027.
We previously showed that palmitoyl-L-carnitine (L-PC) inhibits the Na/K pump current (INa/K). In the present report, we test the hypothesis that L-PC, like ouabain, should increase myocyte shortening. Membrane potentials or ionic currents were recorded simultaneously with cell shortening in single guinea pig ventricular myocytes at room temperature (22 degrees C). Like ouabain, L-PC (1 microM) reversibly depolarized the resting membrane, decreased action potential duration, and increased the amplitude of myocyte contractions. Neither L-PC nor ouabain had a significant effect on Ca current (ICa). When L-PC increased cell shortening during ramp voltage clamp, membrane current shifted inward at voltages negative to -20 mV and shifted outward at more positive voltages. Similar to toxic concentrations of ouabain, L-PC induced transient inward currents and aftercontractions. At concentrations that inhibit INa/K, L-PC acted like ouabain to produce characteristic effects on membrane potentials, currents, and cell contractions that were unrelated to significant changes in ICa. L-PC reduces surface negative charge of erythrocytes and myocytes (C. Gruver and A. J. Pappano, J. Mol. Cell. Cardiol. 25: 1275-1284, 1993), and we speculate that L-PC inhibits INa/K by this mechanism.
我们之前的研究表明,棕榈酰-L-肉碱(L-PC)可抑制钠钾泵电流(INa/K)。在本报告中,我们检验了这样一个假设,即L-PC与哇巴因一样,应该会增加心肌细胞的缩短。在室温(22摄氏度)下,同时记录单个豚鼠心室肌细胞的膜电位或离子电流以及细胞缩短情况。与哇巴因一样,L-PC(1微摩尔)可使静息膜电位可逆性去极化,缩短动作电位持续时间,并增加心肌细胞收缩幅度。L-PC和哇巴因对钙电流(ICa)均无显著影响。当L-PC在斜坡电压钳制期间增加细胞缩短时,膜电流在电压负于-20毫伏时向内移动,在更正的电压时向外移动。与中毒浓度的哇巴因相似,L-PC可诱导瞬时内向电流和后收缩。在抑制INa/K的浓度下,L-PC的作用与哇巴因相似,对膜电位、电流和细胞收缩产生特征性影响,而这些影响与ICa的显著变化无关。L-PC可降低红细胞和心肌细胞表面的负电荷(C.格鲁弗和A.J.帕帕诺,《分子与细胞心脏病学杂志》25: 1275 - 1284, 1993),我们推测L-PC通过这种机制抑制INa/K。