CELLULAR AND SUBCELLULAR CALCIUM ION HOMEOSTASIS

这个项目的重点是细胞如何实现体内平衡的机制 胞浆和其他细胞内的钙离子浓度 脑室，并允许改变钙离子对激素和 神经递质。今年，我们研究了 线粒体内游离钙离子([Ca~(2+)]m)对离体单细胞的刺激作用 电刺激和β-肾上腺素能激动剂作用下的大鼠心肌细胞。 在0至2赫兹范围内增加电刺激的频率， 引起[Ca~(2+)]_m轻度升高：β-肾上腺素能刺激没有 对静止细胞(平均[Ca~(2+)]m=75 nM)的影响，但引起明显的 2赫兹刺激的细胞增加(平均[Ca~(2+)]m从120增加到 570海里)。此外，在非电刺激下，当[Ca~(2+)]m升高时 细胞，例如通过部分Na+替代，~-肾上腺素能刺激没有 效果。因此，肾上腺素能激动剂对[Ca~(2+)]m的影响是通过改变 在收缩时瞬间的钙离子，而不是线粒体的钙离子 运输蛋白本身。近低温刺激下细胞内钙离子浓度的变化 生理频率，即4赫兹，在(约600牛米)范围内 给予大约50%的线粒体脱氢酶刺激。 这个项目是与LCS心脏功能科合作完成的。

This project focuses on the mechanism whereby cells achieve homeostasis of Ca2+ ion concentration, both within the cytosol and other cellular compartments, and allow changes in Ca2+ in response of hormones and neurotransmitters. This year we have studied the response of intramitochondrial free Ca2+ ([Ca2+]m) to stimulation of isolated, single rat cardiac myocytes, both electrically and by beta-adrenergic agonists. Increasing frequency of electrical stimulation, over the range 0 to 2 Hz, caused modest increases in [Ca2+]m: beta-adrenergic stimulation had no effect on the quiescent cell (mean [Ca2+]m = 75 nM) but caused a marked increase in cells stimulated at 2 Hz (mean [Ca2+]m increased from 120 to 570 nM). Further, when [Ca2+]m was raised in non-electrically stimulated cells, e.g. by partial Na+-replacement, ~-adrenergic stimulation had no effect. Thus, the effect of adrenergic agonists on [Ca2+]m is via changes in systolic transients in Ca2+, rather than on the mitochondrial Ca2+ transport proteins per se. Values of [Ca2+]m in cells stimulated at near- physiological frequencies, viz 4 Hz, are in the range (about 600 nM) giving approximately 50% stimulation of mitochondrial dehydrogenases. This project is a collaboration with the Cardiac Function Section, LCS.