Direct effects of apelin on cardiomyocyte contractility and electrophysiology.
Apelin, the ligand for the angiotensin receptor like-1, has been implicated in the pathogenesis of atrial fibrillation and heart failure. However, it is unknown if apelin has direct effects on cardiomyocyte contractility and electrophysiology. APJ-like immunoreactivity was localized to T-tubules and intercalated disc area in isolated adult rat ventricular myocytes. Apelin (1 nM) significantly increased sarcomere shortening in normal as well as failing cardiomyocytes. The transient increase in shortening was not accompanied by increased [Ca(2+)] transient amplitude. Apelin significantly activated the sarcolemmal Na(+)/H(+) exchanger (NHE) and increased intracellular pH. Moreover, apelin (10 nM) increased conduction velocity in monolayers of cultured neonatal rat cardiac myocytes. Our results demonstrate for the first time that apelin has direct effects on the propagation of action potential and contractility in cardiomyocytes. One of the mechanisms involved in the inotropic effect may be an increased myofilament sensitivity to Ca(2+) as apelin enhanced the activity of NHE with consequent intracellular alkalinization.
Farkasfalvi
Klára
K
Heart Science Centre, Laboratory of Cell Electrophysiology, NHLI, Imperial College London, Harefield Hospital, Harefield, Middlesex UB9 6JH, UK.
Stagg
Mark A
MA
Coppen
Steven R
SR
Siedlecka
Urszula
U
Lee
Joon
J
Soppa
Gopal K
GK
Marczin
Nándor
N
Szokodi
István
I
Yacoub
Magdi H
MH
Terracciano
Cesare M N
CM
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000073861:Apelin; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000008:administration & dosage*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D036341:Intercellular Signaling Peptides and Proteins; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
D000073861:Apelin; C498579:Apln protein, rat; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D017923:Sodium-Hydrogen Exchangers; D002118:Calcium