Regulation of L-type calcium channel by intracellular subunit in cardiac hypertrophy and failure.

L型钙通道位于心肌细胞的T小管和小窝中，在兴奋收缩偶联和心肌肥大中起重要作用。LTCC的b2a亚单位(B2a)在心力衰竭中的表达增加。CaMKII对b2a的磷酸化增强了LTCC的活性。在本研究中，我们研究了b2a磷酸化在心肌肥厚中的病理作用。我们开发了一种方法来检测CaMKII的小窝特异性激活，发现b2a磷酸化发生在小窝中，并在A1肾上腺素能刺激下诱导心肌细胞肥大。因此，我们获得了高表达b2a非磷酸化突变体的转基因小鼠(Tg)，突变体和野生型Tg中b2a的表达相似。A1肾上腺素能刺激引起的心肌肥厚在突变型TG小鼠中与野生型TG小鼠相比有所减轻。总而言之，我们发现磷酸化的b2a定位于小窝，并夸大了心肌肥厚。

L-type calcium channel (LTCC) localizes at T-tubules and caveolae in cardiomyocytes, and plays major roles in excitation-contraction coupling and cardiac hypertrophy. The expression of b2a subunit of LTCC (b2a) is increased in human failing heart. Phosphorylation of b2a by CaMKII enhanced LTCC activity. In the present study, we examined the pathological role of b2a phosphorylation in cardiac hypertrophy. We developed a method to examine caveolae-specific activation of CaMKII and found that b2a phosphorylation occurs specifically in caveolae and elicit myocyte hypertrophy in a1 adrenergic stimulation. Thus, we generated transgenic mice (TG) overexpressing non phosphorylated mutant of b2a.The expressions of b2a in both mutant and wild-type TG were similar. a1 adrenergic stimulation induced cardiac hypertrophy was attenuated in mutant TG compared to wild-type TG mice. In conclusion, we revealed that phosphorylated b2a localized at caveolae and exaggerates cardiac hypertrophy.