title: Cardiac receptor activation and arrhythmogenesis.
abstract: New evidence has been accumulated allowing a better understanding of the physiology and pathophysiology of receptors in the heart. Three major receptor systems influence electrophysiological characteristics of myocardial cells and are critical in the development and prevention of cardiac arrhythmias: the adrenergic, the muscarinic and the adenosine systems. Although it has long been recognized that beta adrenergic stimulation is arrhythmogenic, only recently have the mechanisms of this arrhythmogenic effect been clarified. In addition, the contribution to arrhythmogenesis of alpha receptor stimulation, which has been overlooked for many years, has been recognized as an important accompaniment to the beta component, especially during hypoxia-ischaemia. On the other hand, it has been demonstrated that although direct electrophysiological effects of acetylcholine on the ventricle remain controversial, the antagonism of sympathetic activation by cholinergic stimulation may be important in preventing arrhythmias induced by a high sympathetic tone in the presence of myocardial ischaemia. More recently, the importance of the adenosine system has been better appreciated. Experimental studies have shown that adenosine receptor activation inhibits the adenylyl cyclase system by activating the Gi regulatory proteins. Activation of this pathway inhibits the development of adrenergic-dependent triggered activity in isolated cells and these have also been confirmed in man. It is likely that this effect is specific against triggered rhythms induced by adrenergic activation. Even though further research is needed to clarify fully the interaction of these three systems at the subcellular level, the pharmacological modulation of these cardiac receptors appears as a rational approach for refining the treatment of arrhythmias.
authors.affiliation: Centro di Fisiologia Clinica e Ipertensione, Università degli Studi di Milano, Italy.
authors.forename: S G
authors.initials: SG
authors.lastname: Priori
authors.forename: C
authors.initials: C
authors.lastname: Napolitano
authors.forename: P J
authors.initials: PJ
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology*; D006321:Heart / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology; D006801:Humans; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D018047:Receptors, Purinergic P1 / Q000502:physiology; D017180:Tachycardia, Ventricular / Q000503:physiopathology
chemical_list: D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D017981:Receptors, Neurotransmitter; D018047:Receptors, Purinergic P1