Zhou W, Fontenot H J, Liu S, Kennedy R H
Department of Anesthesiology, University of Arkansas for Medical Sciences, Little Rock 72205-7199, USA.
Anesthesiology. 1997 Mar;86(3):670-5. doi: 10.1097/00000542-199703000-00020.
Propofol elicits a rapid depression of transsarcolemmal Ca2+ influx and myocardial contractility. However, the mechanism underlying this action has not been well described. The present study was designed to test the hypothesis that propofol acts as an antagonist of L-type calcium channels.
Experiments monitored effects of propofol on (1) the binding of [3H]nitrendipine (a 1,4-dihydropyridine calcium channel antagonist) to rat myocardial membranes; (2) L-type calcium current (ICa,L) as determined using whole-cell patch-clamp techniques in intact rat cardiomyocytes; and (3) myocardial contractility as examined in isolated rat papillary muscle.
Propofol, in concentrations as low as 6 microM, increased the apparent dissociation constant (Kd) for [3H]nitrendipine without affecting binding-site density (Bmax). This decrease in dihydropyridine-binding affinity was associated with a depressed ICa,L in cardiomyocytes and diminished myocardial contractility. Other experiments showed that etomidate has no effect on [3H]nitrendipine binding, whereas ketamine enhances dihydropyridine binding.
Results suggest that propofol may inhibit cardiac L-type calcium current by interacting with the dihydropyridine-binding site.
丙泊酚可迅速抑制跨肌膜钙离子内流及心肌收缩力。然而，这一作用的潜在机制尚未得到充分描述。本研究旨在验证丙泊酚作为L型钙通道拮抗剂的假说。
实验监测丙泊酚对以下方面的影响：（1）[3H]尼群地平（一种1,4 - 二氢吡啶类钙通道拮抗剂）与大鼠心肌膜的结合；（2）采用全细胞膜片钳技术测定完整大鼠心肌细胞中的L型钙电流（ICa,L）；（3）在离体大鼠乳头肌中检测心肌收缩力。
丙泊酚浓度低至6微摩尔时，可增加[3H]尼群地平的表观解离常数（Kd），而不影响结合位点密度（Bmax）。二氢吡啶结合亲和力的降低与心肌细胞中ICa,L降低及心肌收缩力减弱相关。其他实验表明，依托咪酯对[3H]尼群地平结合无影响，而氯胺酮可增强二氢吡啶结合。
结果提示丙泊酚可能通过与二氢吡啶结合位点相互作用来抑制心脏L型钙电流。
