Horwitz B A, Horowitz J M, Smith R E
Proc Natl Acad Sci U S A. 1969 Sep;64(1):113-20. doi: 10.1073/pnas.64.1.113.
Intracellular potentials of brown fat cells in lightly anesthetized cold-acclimated rats were measured in vivo. The effects of adrenergic agonists and antagonists on these potentials were examined in an attempt to relate the electrical activity of the cells to the adrenergic-induced stimulation of brown fat thermogenesis.Norepinephrine, the physiological mediator of brown fat heat production, significantly depolarized the membrane of these cells in vivo. This was effected either upon norepinephrine administration (3-100 mug/kg body wt) or excitation of the transsected nerve trunk to the interscapular fat pad and appreciably inhibited (55%) by doses of propranolol (1 mg/kg) sufficient to abolish the temperature increase of the tissue. Since theophylline (325 mum/kg) did not depolarize the cells, although it stimulated thermogenesis in the tissue, the depolarizing effect of norepinephrine is interpreted as being at least partially associated with biochemical events terminating in the activation of adenylate cyclase. However, the norepinephrine-induced electrical changes and the ensuing increase in brown fat thermogenesis appear to be causally independent and experimentally separable. On the other hand, our data do not preclude the speculation that the membrane phenomenon, if accompanied by increased Na(+), may serve partially to regulate the metabolic rate of brown fat during long-term physiological stimulation (e.g., cold stress) by increasing the rate of ATP utilization via the Na(+)/K(+) pump.
在轻度麻醉的冷适应大鼠体内测量褐色脂肪细胞的细胞内电位。研究了肾上腺素能激动剂和拮抗剂对这些电位的影响,试图将细胞的电活动与肾上腺素能诱导的褐色脂肪产热刺激联系起来。去甲肾上腺素是褐色脂肪产热的生理介质,在体内可使这些细胞的膜显著去极化。这一效应可通过给予去甲肾上腺素(3 - 100微克/千克体重)或刺激横断至肩胛间脂肪垫的神经干来实现,而给予足以消除组织温度升高的普萘洛尔剂量(1毫克/千克)可明显抑制(55%)这种去极化。由于茶碱(325微摩尔/千克)虽能刺激组织产热,但不会使细胞去极化,所以去甲肾上腺素的去极化作用被解释为至少部分与以腺苷酸环化酶激活为终点的生化事件相关。然而,去甲肾上腺素诱导的电变化以及随之而来的褐色脂肪产热增加似乎在因果关系上是独立的,并且在实验中是可分离的。另一方面,我们的数据并不排除这样一种推测,即如果膜现象伴随着钠离子增加,在长期生理刺激(如冷应激)过程中,它可能通过增加钠钾泵消耗ATP的速率,部分地调节褐色脂肪的代谢率。