Howlett S E, Nicholl P A
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
J Mol Cell Cardiol. 1992 Aug;24(8):885-94. doi: 10.1016/0022-2828(92)91101-a.
To determine whether density and properties of myocardial voltage-sensitive calcium channels may change in the hearts of aged animals, we have compared specific binding of [3H]-nitrendipine ([3H]-NTP) to 1,4-dihydropyridine (DHP) receptors in ventricular homogenate and membrane fractions prepared from the hearts of adult hamsters of different ages. In crude homogenate preparations from young adult animals (70 days) the density (Bmax) of [3H]-NTP binding was 82 +/- 6 fmol/mg protein (n = 5 hearts). By contrast, Bmax values for 400-, 500- and 600-day-old animals were 54 +/- 5, 59 +/- 11 and 50 +/- 2 fmol/mg protein, respectively (significantly lower than control, P = 0.004, n = 4-5 hearts/group). The affinity (Kd) of [3H]-NTP binding was not affected by increasing age. Similar results were obtained in a partially purified membrane fraction. Allosteric modulation of [3H]-NTP binding by the phenylalkylamine, verapamil and the benzothiazepine, diltiazem were preserved in aging heart. These studies demonstrate that the density of myocardial DHP receptors declines in the aged hamster, although the properties of these receptors are unchanged. This suggests that a decrease in voltage-sensitive calcium channels may be associated with normal myocardial aging.
为了确定老年动物心脏中心肌电压敏感性钙通道的密度和特性是否会发生变化，我们比较了不同年龄成年仓鼠心脏制备的心室匀浆和膜组分中[3H] - 尼群地平（[3H] - NTP）与1,4 - 二氢吡啶（DHP）受体的特异性结合。在年轻成年动物（70天）的粗匀浆制备物中，[3H] - NTP结合的密度（Bmax）为82±6 fmol/mg蛋白质（n = 5个心脏）。相比之下，400天、500天和600天龄动物的Bmax值分别为54±5、59±11和50±2 fmol/mg蛋白质（显著低于对照组，P = 0.004，n = 4 - 5个心脏/组）。[3H] - NTP结合的亲和力（Kd）不受年龄增长的影响。在部分纯化的膜组分中也获得了类似的结果。苯烷基胺维拉帕米和苯并硫氮䓬地尔硫䓬对[3H] - NTP结合的变构调节在衰老心脏中得以保留。这些研究表明，老年仓鼠心肌DHP受体的密度下降，尽管这些受体的特性未发生变化。这表明电压敏感性钙通道的减少可能与正常心肌衰老有关。
