Interaction of alpha-and beta-adrenergic activation in the calcium dynamics in mouse brown adipocyte

在棕色脂肪细胞中，-肾上腺素能激活引起Ca^<2+>从内质网（ER）释放和储存操作的Ca^<2+>进入（SOC）。-肾上腺素能激活通过氧化磷酸化解偶联导致线粒体Ca^<2+>释放，氧化磷酸化激活Ca^<2+>诱导的Ca^<2+>从内质网、SOC释放，以及一个新的解偶联的Ca^<2+>入口。我们通过荧光法记录细胞质Ca^<2+>([Ca^<2+>]_i)、线粒体膜电位和内质网Ca^<2+>浓度（[Ca^<2+>]_<ER>），研究了这两种肾上腺素能Ca^<2+>信号通路的相互作用。苯肾上腺素引起的[Ca^<2+>]_i升高和[Ca^<2+>]_<ER>降低在a-激动剂BRL37344的充分作用下被抑制，而在BRL37344的弱作用下被增强。另一方面，BRL37344诱导的[Ca^<2+>]_i双相或三相升高的第二和/或第三组分在阈下浓度的苯肾上腺素的作用下被抑制。因此，当作用强到足以引起[Ca^<2+>]_i的大幅升高时，由于ER中Ca^<2+>含量的降低，在作用后期被抑制。另一方面，当可能是由于IP_3浓度上升不足，作用弱到不足以从内质网释放Ca^<2+>时，线粒体Ca^<2+>释放升高的[Ca^<2+>]_i会促进内质网膜上IP_3受体的激活。

In brown adipocytes,-adrenergic activation evokes Ca^<2+> release from the endoplasmic reticulum(ER) and store-operated Ca^<2+> entry(SOC) in brown adipocytes, while.-adrenergic activation causes mitochondrial Ca^<2+> release via uncoupling of oxidative phosphorylation, which activates Ca^<2+>-induced Ca^<2+> release from the ER, SOC, and a novel uncoupling-linked Ca^<2+> entry. We studied how these two modes of adrenergic Ca^<2+> signaling pathways interact with each other by recording cytoplasmic Ca^<2+>([Ca^<2+>]_i), mitochondrial membrane potential and the Ca^<2+> concentration in the ER([Ca^<2+>]_<ER>) by fluorometry. The rise in [Ca^<2+>]_i and the reduction of [Ca^<2+>]_<ER> evoked by phenylephrine was depressed under the full effect of a-agonist, BRL37344, while they were enhanced under the weak action of BRL37344.On the other hand, the second and/or third components of the bi-or triphasic rises in [Ca^<2+>]_i induced by BRL37344 was depressed under the effect of the subthreshold concentration of phenylephrine. Thus, when the-action is strong enough to cause a large rise in [Ca^<2+>]_i, it was suppressed during the late phase of the-action for the decreased Ca^<2+> content in the ER. On the other hand, when the-action is weak not enough to release Ca^<2+> from the ER presumably due to an inadequate rise in IP_3 concentration, the rises in [Ca^<2+>]_i by mitochondrial Ca^<2+> release would boost the activation of IP_3 receptor at the ER membrane.