Yasui K, Palade P
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77555-0641, USA.
Am J Physiol. 1996 Feb;270(2 Pt 1):C645-9. doi: 10.1152/ajpcell.1996.270.2.C645.
Sphingosine, an endogenous phospholipid known to produce significant decreases in myoplasmic Ca2+ transients, was shown to have a pronounced inhibitory effect on inward Na+ and L-type Ca2+ currents in rat ventricular myocytes. Sphingosine action was accompanied by a slowing of inactivation of both kinds of current. Both sphingosine and sphingosylphosphorylcholine (SPC) caused depolarizing shifts in the activation curves for the two channels. In tests on Ca2+ currents, sphingosine neither showed high affinity for inactivated states nor exhibited any use dependence. The mechanism of the blocking action of sphingosine does not appear to involve effects on bulk surface charge or, at least for Ca2+ channels, a voltage-dependent block. Instead, the results appear most consistent with an effect of sphingosine on channel gating. The shift in the voltage dependence of channel activation by sphingosine and SPC appears likely to be a feature of both the hydrocarbon chains and the net positive charge of these amphiphiles.
鞘氨醇是一种内源性磷脂，已知它能使肌浆内Ca2+瞬变显著减少，研究表明其对大鼠心室肌细胞的内向Na+电流和L型Ca2+电流有明显的抑制作用。鞘氨醇的作用伴随着两种电流失活的减慢。鞘氨醇和鞘氨醇磷酸胆碱（SPC）均使两种通道的激活曲线发生去极化偏移。在对Ca2+电流的测试中，鞘氨醇对失活状态既无高亲和力，也无任何使用依赖性。鞘氨醇的阻断作用机制似乎不涉及对表面总电荷的影响，至少对于Ca2+通道而言，不是电压依赖性阻断。相反，结果似乎最符合鞘氨醇对通道门控的影响。鞘氨醇和SPC引起的通道激活电压依赖性的偏移似乎是这些两亲分子的烃链和净正电荷的共同特征。
