The activity of protein phosphatase 2A (PP2A) is determined by the expression and localization of the regulatory B-subunits. PP2A-B56α is the dominant isoform of the B'-family in the heart. Its role in regulating the cardiac response to β-adrenergic stimulation is not yet fully understood. We therefore generated mice deficient in B56α to test the functional cardiac effects in response to catecholamine administration versus corresponding wild-type (WT) mice. We found the decrease in basal PP2A activity in hearts of knockout (KO) mice was accompanied by a counterregulatory increase in the expression of B' subunits (β and γ) and higher phosphorylation of sarcoplasmic reticulum (SR) Ca²⁺ regulatory and myofilament proteins. The higher phosphorylation levels were associated with enhanced intraventricular pressure and relaxation in catheterized KO mice. In contrast, at the cellular level, we detected depressed Ca²⁺ transient and sarcomere shortening parameters in KO mice at basal conditions. Consistently, the peak amplitude of the L-type Ca²⁺ current (LTCC) was reduced and the inactivation kinetics of I_CaL were prolonged in KO cardiomyocytes. However, we show β-adrenergic stimulation resulted in a comparable peak amplitude of Ca²⁺ transients and myocellular contraction between KO and WT cardiomyocytes. Therefore, we propose higher isoprenaline-induced Ca²⁺ spark frequencies might facilitate the normalized Ca²⁺ signaling in KO cardiomyocytes. In addition, the application of isoprenaline was associated with unchanged LTCC parameters between both groups. Our data suggest an important influence of PP2A-B56α on the regulation of Ca²⁺ signaling and contractility in response to β-adrenergic stimulation in the myocardium.

蛋白磷酸酶 2A (PP2A) 的活性由调节性 B 亚基的表达和定位决定。PP2A-B56α 是心脏中 B' 家族的主要同工型。它在调节心脏对 β-肾上腺素能刺激反应中的作用尚未完全清楚。因此，我们生成了缺乏 B56α 的小鼠，以测试响应于儿茶酚胺给药与相应的野生型 (WT) 小鼠的功能性心脏效应。我们发现敲除 (KO) 小鼠心脏基础 PP2A 活性的降低伴随着 B' 亚基 (β 和 γ) 表达的反调节增加和肌浆网 (SR) Ca ^{2+的更高磷酸化}调节蛋白和肌丝蛋白。较高的磷酸化水平与插入导管的 KO 小鼠的心室内压力和松弛有关。相反，在细胞水平上，我们在基础条件下检测到 KO 小鼠的Ca ^{2+瞬态和肌节缩短参数降低。}一致地，L型Ca ²⁺电流（LTCC）的峰值幅度降低并且I _CaL的失活动力学在KO心肌细胞中延长。然而，我们显示β-肾上腺素能刺激导致可比的Ca ²⁺瞬变峰值幅度和KO 和WT 心肌细胞之间的肌细胞收缩。因此，我们提出更高的异丙肾上腺素诱导的 Ca ²⁺火花频率可能有助于 KO 心肌细胞中标准化的 Ca ²⁺信号传导。此外，异丙肾上腺素的应用与两组之间的 LTCC 参数不变有关。我们的数据表明 PP2A-B56α 对心肌中 β-肾上腺素能刺激对 Ca ²⁺信号传导和收缩性的调节具有重要影响。