TY - JOUR
T1 - Neurokinin-3 receptor activation selectively prolongs atrial refractoriness by inhibition of a background K+ channel
AU - Veldkamp, Marieke W.
AU - Geuzebroek, Guillaume S. C.
AU - Baartscheer, Antonius
AU - Verkerk, Arie O.
AU - Schumacher, Cees A.
AU - Suarez, Gedeon G.
AU - Berger, Wouter R.
AU - Casini, Simona
AU - van Amersfoorth, Shirley C. M.
AU - Scholman, Koen T.
AU - Driessen, Antoine H. G.
AU - Belterman, Charly N. W.
AU - van Ginneken, Antoni C. G.
AU - de Groot, Joris R.
AU - de Bakker, Jacques M. T.
AU - Remme, Carol Ann
AU - Boukens, Bas J.
AU - Coronel, Ruben
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85055078631&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30341287
U2 - https://doi.org/10.1038/s41467-018-06530-5
DO - https://doi.org/10.1038/s41467-018-06530-5
M3 - Article
C2 - 30341287
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4357
ER -