Voĭtychuk O I, Asmolkova V S, Hula N M, Oz M, Shuba Ia M
Fiziol Zh (1994). 2010;56(5):13-22.
The group of N-acylethanolamines (NAE) includes lipids that are capable of modulating plasma membrane ion channels without involvement of cannabinoid receptors. However, the action of various members of NAE on voltage-gated Na+ channels (VGSC) in cardiac tissue is still not fully elucidated. Here using patch-clamp technique we have studied the modulation of biophysical properties of VGSC of neonatal cardiomyocytes by saturated N-stearoylethanolamine (NSE) and monounsaturated N-oleoylethanolamine (OEA). NSE in 1-200 tM concentration range did not significantly alter the amplitude of inward Na+ current (I(Na)), but 100 microM NSE shifted its steady-state activation and inactivation curves in hyperpolarization direction by 2.4 mV and 10.6 mV, respectively. Activation kinetics of the current was not changed by NSE, but its inactivation was accelerated by about 1.2-fold in the -60 - -30 mV range of membrane potentials. Unlike NSE, OEA dose-dependently inhibited I(Na) with kappa(D) = 11.4 +/- 1.6 microM and maximal block at saturating concentration of 30 +/- 3%. It also stronger than NSE shifted current's steady-state activation and inactivation curves (-6.4 mV and -14.0 mV, respectively, at 100 microM) in hyperpolarization direction. The effect of OEA on I(Na) activation kinetics was negligible, but it more pronouncedly than NSE accelerated inactivation of the current. Thus, both members of NAE influence the voltage-dependence of activation, inactivation and kinetics of I(Na). These effects were more prominent for monounsaturated OEA, which also partially blocked I(Na). The discovered effects of NSE and OEA on VGSCs may in part be responsible for the decrease of cardiomycytes' excitability by these lipids under normal as well as pathologic conditions.
N-酰基乙醇胺（NAE）组包括能够在不涉及大麻素受体的情况下调节质膜离子通道的脂质。然而，NAE的各种成员对心脏组织中电压门控Na+通道（VGSC）的作用仍未完全阐明。在这里，我们使用膜片钳技术研究了饱和N-硬脂酰乙醇胺（NSE）和单不饱和N-油酰乙醇胺（OEA）对新生心肌细胞VGSC生物物理特性的调节作用。浓度在1-200 tM范围内的NSE没有显著改变内向Na+电流（I(Na)）的幅度，但100 microM的NSE分别将其稳态激活和失活曲线向超极化方向移动了2.4 mV和10.6 mV。NSE没有改变电流的激活动力学，但其失活在-60至-30 mV的膜电位范围内加速了约1.2倍。与NSE不同，OEA剂量依赖性地抑制I(Na)，解离常数kappa(D)=11.4±1.6 microM，在饱和浓度30±3%时达到最大阻断。它还比NSE更强烈地将电流的稳态激活和失活曲线（在100 microM时分别为-6.4 mV和-14.0 mV）向超极化方向移动。OEA对I(Na)激活动力学的影响可以忽略不计，但它比NSE更明显地加速了电流的失活。因此，NAE的两个成员都影响I(Na)激活、失活和动力学的电压依赖性。这些效应对于单不饱和OEA更为突出，OEA也部分阻断了I(Na)。NSE和OEA对VGSCs的发现效应可能部分解释了在正常和病理条件下这些脂质导致心肌细胞兴奋性降低的原因。
