TY - JOUR
T1 - Ionic mechanisms underlying the effects of Vasoactive intestinal polypeptide on canine atrial myocardium
AU - Xi, Yutao
AU - Wu, Geru
AU - Ai, Tomohiko
AU - Cheng, Nancy
AU - Kalisnik, Jurij Matija
AU - Sun, Junping
AU - Abbasi, Shahrzad
AU - Yang, Donghui
AU - Fan, Christopher
AU - Yuan, Xiaojing
AU - Wang, Suwei
AU - Elayda, Macarthur
AU - Gregoric, Igor D.
AU - Kantharia, Bharat K.
AU - Lin, Shien Fong
AU - Cheng, Jie
PY - 2013/10
Y1 - 2013/10
N2 - Background: Vasoactive intestinal polypeptide (VIP) is released from intracardiac neurons during vagal stimulation, ischemia, and heart failure, which are associated with increased vulnerability to atrial fibrillation. VIP shortens atrial effective refractory periods in dogs. Endogenous VIP contributes to vagally mediated acceleration of atrial electric remodeling. VIP is also shown to prolong the duration of acetylcholine-induced atrial fibrillation. However, the ionic mechanisms underlying VIP effects are largely unknown. Methods and Results: The effects of VIP on transmembrane ion channels were studied in canine atrial cardiomyocytes using patch-clamp techniques. VIP increased delayed rectifier K+ current and L-type calcium current but decreased the transient outward K+ current and sodium current. Optical mapping technique was used to assess effects of VIP on action potential durations (APDs) in isolated canine left atria. VIP shortened APD and slowed conduction velocity in a dosedependent manner. Furthermore, VIP increased spatial heterogeneity of APD and conduction velocity, as assessed by the SDs of APD and conduction velocity, and atrial fibrillation inducibility. Conclusions: Through its diverse effects on ion channels, VIP shortens APD with increased APD spatial heterogeneity and decreases intra-atrial conduction velocity, which may play an important role in the pathogenesis of atrial arrhythmias in scenarios where VIP release is increased.
AB - Background: Vasoactive intestinal polypeptide (VIP) is released from intracardiac neurons during vagal stimulation, ischemia, and heart failure, which are associated with increased vulnerability to atrial fibrillation. VIP shortens atrial effective refractory periods in dogs. Endogenous VIP contributes to vagally mediated acceleration of atrial electric remodeling. VIP is also shown to prolong the duration of acetylcholine-induced atrial fibrillation. However, the ionic mechanisms underlying VIP effects are largely unknown. Methods and Results: The effects of VIP on transmembrane ion channels were studied in canine atrial cardiomyocytes using patch-clamp techniques. VIP increased delayed rectifier K+ current and L-type calcium current but decreased the transient outward K+ current and sodium current. Optical mapping technique was used to assess effects of VIP on action potential durations (APDs) in isolated canine left atria. VIP shortened APD and slowed conduction velocity in a dosedependent manner. Furthermore, VIP increased spatial heterogeneity of APD and conduction velocity, as assessed by the SDs of APD and conduction velocity, and atrial fibrillation inducibility. Conclusions: Through its diverse effects on ion channels, VIP shortens APD with increased APD spatial heterogeneity and decreases intra-atrial conduction velocity, which may play an important role in the pathogenesis of atrial arrhythmias in scenarios where VIP release is increased.
KW - Action potentials
KW - Atrial fibrillation
KW - Ion channels
KW - Vasoactive intestinal polypeptide
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U2 - 10.1161/CIRCEP.113.000518
DO - 10.1161/CIRCEP.113.000518
M3 - Article
C2 - 24046327
AN - SCOPUS:84891546948
SN - 1941-3149
VL - 6
SP - 976
EP - 983
JO - Circulation: Arrhythmia and Electrophysiology
JF - Circulation: Arrhythmia and Electrophysiology
IS - 5
ER -