Activation of Sarcolemmal α2 Adrenoceptors Supports Са2+ Homeostasis and Prevents Ventricular Arrhythmia under Sympathetic Stress

Abstract

Abstract—The body’s response to stress is mediated by the interaction of catecholamines with adrenergic α- and β-receptors. It has been established that, in contrast to α1- and β-adrenoceptors, α2-adrenoceptors are involved in feedback loops of the simpatoadrenal system, which controls the release of catecholamines (norepinephrine and epinephrine) to save energy resources and the function of peripheral organs under an overload of catecholamines. Violations of the feedback mechanisms lead to various pathologies, including hypertrophic heart remodeling, followed by the development of heart failure. We previously found the expression of α2-adrenoreceptors in the plasma membrane of cardiomyocytes, where they participate in the regulation of the intracellular level of Ca2+. We suggested that these receptors are able to locally control the response of the heart muscle to stress in addition to the traditional mechanism. We have shown in this study that sarcolemmal α2-adrenoreceptors attenuate the positive inotropic effect of adrenergic stimulation in papillary muscles by controlling the level of free Ca2+ in cytosol. The ability of α2-adrenoreceptor agonists to suppress intracellular spontaneous Ca2+ oscillations increases the efficiency of systolic function of papillary muscles and reduces the likelihood of dangerous ventricular arrhythmia. Thus, α2-adrenoreceptors in the sarcolemmal membrane of cardiomyocytes have their own protective potential, which can prevent pathological remodeling of the heart muscle under chronic stress.