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内质网(ER)的钙释放和储存操作的钙进入(SOC)，而-肾上腺素能激活通过氧化磷酸化解偶联引起线粒体钙释放，氧化磷酸化激活激活内质网(ER)诱导的钙释放和一种新的解偶联的钙离子进入。我们通过荧光分光光度法记录细胞内钙离子、线粒体膜电位和内质网内钙离子浓度，研究了这两种肾上腺素能钙信号通路是如何相互作用的。苯肾上腺素诱发的[Ca^&lt；2+&gt；]_i升高和[Ca^&lt；2+&gt；]_ER&gt；降低在α-激动剂BRL37344的完全作用下被抑制，而在BRL37344的弱作用下被增强。在亚阈值浓度下，BRL37344引起的[Ca^&lt；2+&gt；]_i的第二和/或三相升高被抑制。因此，当-作用强到足以引起[Ca^&lt；2+&gt；]_i的大幅上升时，它在-作用的后期被抑制，因为内质网中的Ca^&lt；2+&gt；含量降低。另一方面，当这种作用很弱而不足以从内质网释放时，可能是由于IP_3浓度升高所致，线粒体释放的[Ca^&lt；2+&gt；]_i将促进内质网膜上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.