In heart failure, β-adrenergic receptor (β-AR)-Gsα-cAMP-protein kinase A (PKA) signalling predisposes to delayed-afterdepolarisation-mediated arrhythmias. Phosphodiesterases (PDEs) hydrolyse cAMP, and PDE3 restrains β 1 -AR, β 2 -AR-mediated inotropic responses in failing hearts from β-blocker-treated patients. Whether these receptors provoke arrhythmias through ryanodine receptor (RyR2) dysregulation, and how PDE activity and...

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) cultured in the presence of retinoic acid were proposed as a model for human atrium. Since in the human heart positive inotropic effects of serotonin (5-HT) are restricted to the atrium, we investigated whether the presence of 5-HT responses may distinguish between hiPSC-atrial and ventricular CM. Nonfiltered retinoic acid (1 µM) was used to induce an atrial...

This review summarises the major contributions of Alberto J. Kaumann who died in December 2024. The German-born pharmacologist devoted his scientific life to the cardiovascular adrenergic and serotinergic systems. He classified the subtypes of the cardiac β-adrenoceptors (β-AR) into β 1 - and β 2 -AR using the subtype-selective antagonist. In addition, he showed that the dual coupling of β 2 -AR to Gα s - and Gα i -proteins pl...

Sex-related differences in cardiac electrophysiology are well established in the ventricle and have reached textbook level. In contrast, our understanding of sex effects in the human atrium remains limited, despite clear clinical observations such as the lower incidence of atrial fibrillation (AF) in women. In this review, we summarize sex differences and discuss potential reasons for the imbalance in knowledge, including the...

Optogenetic actuators are rapidly advancing tools used to control physiology in excitable cells, such as neurons and cardiomyocytes. In neuroscience, these tools have been used to either excite or inhibit neuronal activity. Cell type–targeted actuators have allowed to study the function of distinct cell populations. Whereas the first described cation channelrhodopsins allowed to excite specific neuronal cell populations, anion...

Atrial fibrillation (AF)–associated remodeling includes contractile dysfunction whose reasons are only partially resolved. Serotonin (5-HT) increases contractile force and causes arrhythmias in atrial trabeculae from patients in sinus rhythm (SR). In persistent atrial fibrillation (peAF), the force responses to 5-HT are blunted and arrhythmic effects are abolished. Since force but not arrhythmic responses to 5-HT in peAF could...