Neurokinin-3 receptor activation selectively prolongs atrial refractoriness by inhibition of a background K + channel.

Autor:	Veldkamp MW; Department of Clinical and Experimental Cardiology, Heart Center, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. m.w.veldkamp@amc.uva.nl., Geuzebroek GSC; Department of Cardiothoracic Surgery, RadboudUMC, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands., Baartscheer A; Department of Clinical and Experimental Cardiology, Heart Center, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Verkerk AO; Department of Medical Biology, Academic Medical Center Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Schumacher CA; Department of Clinical and Experimental Cardiology, Heart Center, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Suarez GG; Biomedical Sciences VU University Medical Center, De Boelelaan 1105, 1081 HV, Amsterdam, The Netherlands., Berger WR; Department of Clinical and Experimental Cardiology, Heart Center, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Casini S; Department of Clinical and Experimental Cardiology, Heart Center, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., van Amersfoorth SCM; Department of Clinical and Experimental Cardiology, Heart Center, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Scholman KT; Department of Medical Biology, Academic Medical Center Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Driessen AHG; Department of Cardiothoracic Surgery, Heart Center, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Belterman CNW; Department of Clinical and Experimental Cardiology, Heart Center, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., van Ginneken ACG; Department of Medical Biology, Academic Medical Center Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., de Groot JR; Department of Clinical and Experimental Cardiology, Heart Center, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., de Bakker JMT; Department of Clinical and Experimental Cardiology, Heart Center, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Remme CA; Department of Clinical and Experimental Cardiology, Heart Center, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Boukens BJ; Department of Medical Biology, Academic Medical Center Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Coronel R; Department of Clinical and Experimental Cardiology, Heart Center, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.; L'Institut de RYthmologie et de Modélisation Cardiaque (LIRYC), Fondation Université Bordeaux, Avenue du Haut Lévêque-33604 Pessac cedex, Bordeaux, France.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2018 Oct 19; Vol. 9 (1), pp. 4357. Date of Electronic Publication: 2018 Oct 19.
DOI:	10.1038/s41467-018-06530-5
Abstrakt:	The cardiac autonomic nervous system (ANS) controls normal atrial electrical function. The cardiac ANS produces various neuropeptides, among which the neurokinins, whose actions on atrial electrophysiology are largely unknown. We here demonstrate that the neurokinin substance-P (Sub-P) activates a neurokinin-3 receptor (NK-3R) in rabbit, prolonging action potential (AP) duration through inhibition of a background potassium current. In contrast, ventricular AP duration was unaffected by NK-3R activation. NK-3R stimulation lengthened atrial repolarization in intact rabbit hearts and consequently suppressed arrhythmia duration and occurrence in a rabbit isolated heart model of atrial fibrillation (AF). In human atrial appendages, the phenomenon of NK-3R mediated lengthening of atrial repolarization was also observed. Our findings thus uncover a pathway to selectively modulate atrial AP duration by activation of a hitherto unidentified neurokinin-3 receptor in the membrane of atrial myocytes. NK-3R stimulation may therefore represent an anti-arrhythmic concept to suppress re-entry-based atrial tachyarrhythmias, including AF.
Databáze:	MEDLINE
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