Non-neuronal ventricular cardiomyocyte-located nicotinergic acetylcholine receptors cause remodelling and arrhythmias

Graphical AbstractThe neuronal and non-neuronal cholinergic system in the heart. Abnormal autonomic nervous system activation leads to arrhythmias by altering cardiac action potential duration (APD) and conduction velocity, causing rotor stabilization and arrhythmias. ACh released from cardiomyocytes binds to nicotinergic ACh receptors (nAChRs) to depolarize resting membrane potential, resulting in triggered activity and conduction disturbances that may lead to reentry. For further details, see the text. Upward and downward arrows indicate the direction of change. AChE, acetylcholinesterase; CHT; choline transporter; ChAT, choline acetyltransferase; α/βAR, alpha and beta adrenoceptors; IK,ACh, ACh-activated K+-current; NET, norepinephrine transporter, M2R, muscarinic receptor type-2; SAN, sinoatrial node; AVN, atrioventricular node; Gs, stimulatory G-protein; Gi/o, inhibitory G-protein; cAMP, cyclic adenosine monophosphate; EADs, early afterdepolarizations; DADs, delayed afterdepolarizations.Open in new tabDownload slide