COMPARISON BETA2 VS BETA1 ADRENOCEPTOR STIMULATION IN RAT CARDIOCYTE STIMULATION

心脏中存在β1和β2肾上腺素能受体。而当 前者的细胞效应得到了广泛的研究，其具体效应 后者尚未得到澄清。我们研究了Beta2-和 β_1-肾上腺素能受体激动剂对细胞内钙离子的影响 (CaI)瞬变，以Indo-1荧光的瞬时增加为指标 激励后的比率，抽动幅度，通过光电二极管测量 阵列，膜电位和L型肌膜钙电流，以及 全细胞膜片电极法测定大鼠单个心室肌细胞内钙离子浓度 肌细胞。选择性β2AR激动剂津替洛尔(Zint)增加 在一个浓度范围内，蔡瞬变和抽动的幅度- 依赖的态度。当Beta2AR的 选择性地刺激异丙肾上腺素(ISO)的存在 β1AR拮抗剂，CGP 20712A(CGP)。β-1AR刺激 去甲肾上腺素(NE)增加抽动幅度的程度与 Beta2AR。然而，几个显著的区别是，对 观察β1受体和β2受体的刺激作用。Beta1AR刺激有一个 有效缩短抽动收缩的时间进程， 刺激β-2AR不能缩短脑缺血再灌注损伤的时间进程。 CAI是一过性的，对抽动持续时间的影响很小。为. 在抽动幅度增加的情况下，刺激Beta1ar导致更大的 CAI短暂性增加，提示CAI肌丝减少 互动。β_1AR，但不是β_2AR刺激，可诱发自发性CAI 振荡，增加舒张期Indo-荧光水平，并导致 静息细胞长度的下降。Beta1AR和Beta2AR在 它们对ICA的影响。而同时刺激β1AR和β2AR 增加ICA峰值，β2显著延长ICA 停用时间。因此，刺激Beta2AR延长了这一作用 潜在持续时间比刺激Beta1AR的程度更大。CPT CAMP模拟NE刺激的β-AR效应，但不是那些应有的效应 对β-2AR的刺激。这些结果清楚地表明，两者的Beta2AR 和β1AR肾上腺素能受体在功能上共存于大鼠心室 肌细胞，但这些受体亚型的刺激引起 在离子通道水平上本质上不同的细胞反应， 肌丝和肌浆网(SR)。

Bolus beta1 and beta2 adrenoceptors exist in the heart. While the cellular effects of the former are widely studied, the specific effects of the later have not been elucidated. We studied the effects of beta2- and beta1-adrenoceptor (beta2AR and beta1AR) agonists on the cytosolic Ca2+ (Cai) transient, indexed by the transient increase in Indo-1 fluorescence ratio following excitation, twitch amplitude, measured via photodiode array, and membrane potential and L-type sarcolemmal Ca2+ current, and ICa, measured by whole cell patch electrode in single rat ventricular myocytes. The selective beta2AR agonist Zinterol (Zint) increased the amplitudes of both the Cai transient and twitch in a concentration- dependent manner. Similar results were obtained when beta2AR's were stimulated with isoproterenol (ISO) in the presence of the selective beta1AR antagonist, CGP 20712A (CGP). Beta1AR stimulation induced by norepinephrine (NE) increased twitch amplitude to about the same extent as beta2AR. However, several striking differences between response to beta1AR and beta2AR stimulation were observed. Beta1AR stimulation had a potent effect to abbreviate the time course of the twitch contraction and Cai transient; beta2AR stimulation did not reduce the time course of the Cai transient and had only a minor effect on the twitch duration. For a given increase in twitch amplitude, beta1AR stimulation caused a greater increase in Cai transient, suggesting a diminished Cai-myofilament interaction. beta1AR, but not beta2AR stimulation, evoked spontaneous Cai oscillations, increased the diastolic indo-fluorescence level and caused a decline in resting cell length. Beta1AR and beta2AR also differed in their effects on ICa. While both beta1AR and beta2AR stimulation increased the peak ICa amplitude, beta2 markedly prolonged the ICa inactivation time. Accordingly, beta2AR stimulation prolonged the action potential duration to a greater extent than beta1AR stimulation did. CPT cAMP mimicked the effects of beta1AR stimulation by NE but not those due to beta2AR stimulation. These results clearly indicate that both beta2AR and beta1AR adrenoceptors functionally coexist in rat ventricular myocytes, but that stimulation of these receptor subtypes elicits qualitatively different cell responses at the levels of ionic channels, the myofilaments, and sarcoplasmic reticulum (SR).