Modulation of canine cardiac sodium current by Apelin.
Apelin, a ligand of the G protein-coupled putative angiotensin II-like receptor (APJ-R), exerts strong vasodilating, cardiac inotropic and chronotropic actions. Its expression is highly up-regulated during heart failure. Apelin also increases cardiac conduction speed and excitability. While our knowledge of apelin cardiovascular actions is growing, our understanding of the physiological mechanisms behind the cardiac effects remains limited. We tested the effects of apelin on the cardiac sodium current (I(Na)) using patch clamp technique on cardiac myocytes acutely dissociated from dog ventricle. We found that apelin-13 and apelin-17 increased peak I(Na) by 39% and 61% and shifted its mid-activation potential by -6.8+/-0.6 mV and -17+/-1 mV respectively thus increasing channel opening at negative voltage. Apelin also slowed I(Na) recovery from inactivation. The effects of apelin on I(Na) amplitude were linked to activation of protein kinase C. Apelin also increased I(Na) "window" current by up to 600% suggesting that changes in intracellular sodium may contribute to the apelin inotropic effects. Our results reveal for the first time the effects of apelin on I(Na). These effects are likely to modulate cardiac conduction and excitability and may have beneficial antiarrhythmic action in sodium chanelopathies such as Brugada Syndrome where I(Na) amplitude is reduced.
Chamberland
Caroline
C
Department of Physiology and Biophysics, Université de Sherbrooke, Sherbrooke, Qc., Canada.
Barajas-Martinez
Hector
H
Haufe
Volker
V
Fecteau
Marie-Hélène
MH
Delabre
Jean-Francois
JF
Burashnikov
Alexander
A
Antzelevitch
Charles
C
Lesur
Olivier
O
Chraibi
Ahmed
A
Sarret
Philippe
P
Dumaine
Robert
R
D000200:Action Potentials; D000818:Animals; D000073861:Apelin; D002352:Carrier Proteins / Q000494:pharmacology*; D004285:Dogs; D004594:Electrophysiology / Q000379:methods; D006321:Heart / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010496:Pericardium / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000737:chemistry*; D015222:Sodium Channels / Q000737:chemistry
D000073861:Apelin; C498579:Apln protein, rat; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D015222:Sodium Channels; D012964:Sodium