Coupling of β 2 -Adrenoceptor to G i Proteins and Its Physiological Relevance in Murine Cardiac Myocytes

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Abstract
—Transgenic mouse models have been developed to manipulate β-adrenergic receptor (βAR) signal transduction. Although several of these models have altered βAR subtypes, the specific functional sequelae of βAR stimulation in murine heart, particularly those of β2-adrenergic receptor (β2AR) stimulation, have not been characterized. In the present study, we investigated effects of β2AR stimulation on contraction, [Ca2+]i transient, and L-type Ca2+ currents (ICa) in single ventricular myocytes isolated from transgenic mice overexpressing human β2AR (TG4 mice) and wild-type (WT) littermates. Baseline contractility of TG4 heart cells was increased by 3-fold relative to WT controls as a result of the presence of spontaneous β2AR activation. In contrast, β2AR stimulation by zinterol or isoproterenol plus a selective β1-adrenergic receptor (β1AR) antagonist CGP 20712A failed to enhance the contractility in TG4 myocytes, and more surprisingly, β2AR stimulation was also ineffective in increasing contractility...