Foerster Katharina, Kaeferstein Tomas, Groner Ferdi, Engelhardt Stefan, Matthes Jan, Koch Walter J, Lohse Martin J, Herzig Stefan
Department of Pharmacology, University of Cologne, Gleueler Strasse 24, 50931 Cologne, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2004 May;369(5):490-5. doi: 10.1007/s00210-004-0928-3. Epub 2004 Apr 9.
Cardiac effects of catecholamines on the L-type calcium channel depend on beta-adrenoceptor subtype (beta(1)- vs. beta(2)-adrenoceptor). Chronic overexpression of these receptors leads to hypertrophy and early death at moderate (beta(1)) or excessive (beta(2)) levels of overexpression respectively. In order to examine the role of L-type calcium channels in altered cardiomyocyte calcium homeostasis found with beta(1)-adrenoceptor overexpression, and to understand the quantitative differences between beta-adrenoceptor subtypes regarding calcium channel regulation, we examined single channels in myocytes obtained from beta(1)- and beta(2)-adrenoceptor transgenic mice. The effects of the agonist isoproterenol were investigated and compared with acute receptor stimulation in the respective non-transgenic littermates. Channels from beta(1)-adrenoceptor transgenic mice have normal baseline activity, and channel number is not reduced. This contrasts to previous findings with beta(2)-adrenoceptor transgenic mice, where channel activity is depressed. Isoproterenol is unable to stimulate channel activity in both transgenic models. In conclusion, the L-type calcium channel is not likely to be involved in alterations of calcium handling of beta(1)-adrenoceptor transgenic myocytes. Furthermore, chronic beta(1)-adrenoceptor overexpression does not depress channel activity, giving another example of the difference between beta(1)- and beta(2)-adrenoceptor signal transduction.
儿茶酚胺对L型钙通道的心脏效应取决于β-肾上腺素能受体亚型（β1-与β2-肾上腺素能受体）。这些受体的慢性过表达分别在适度（β1）或过度（β2）过表达水平时导致心肌肥大和早期死亡。为了研究L型钙通道在β1-肾上腺素能受体过表达时心肌细胞钙稳态改变中的作用，并了解β-肾上腺素能受体亚型在钙通道调节方面的定量差异，我们检测了从β1-和β2-肾上腺素能受体转基因小鼠获得的心肌细胞中的单通道。研究了激动剂异丙肾上腺素的作用，并与相应非转基因同窝小鼠中的急性受体刺激进行了比较。来自β1-肾上腺素能受体转基因小鼠的通道具有正常的基线活性，且通道数量未减少。这与先前β2-肾上腺素能受体转基因小鼠的研究结果形成对比，在后者中通道活性受到抑制。异丙肾上腺素在两种转基因模型中均无法刺激通道活性。总之，L型钙通道不太可能参与β1-肾上腺素能受体转基因心肌细胞钙处理的改变。此外，慢性β1-肾上腺素能受体过表达不会抑制通道活性，这为β1-和β2-肾上腺素能受体信号转导之间的差异提供了另一个例子。
