title: Lysophosphatidic acid increases the electrophysiological instability of adult rabbit ventricular myocardium by augmenting L-type calcium current.
abstract: Lysophosphatidic acid (LPA) has diverse actions on the cardiovascular system and is widely reported to modulate multiple ion currents in some cell types. However, little is known about its electrophysiological effects on cardiac myocytes. This study investigated whether LPA has electrophysiological effects on isolated rabbit myocardial preparations. The results indicate that LPA prolongs action potential duration at 90% repolarization (APD(90)) in a concentration- and frequency-dependent manner in isolated rabbit ventricular myocytes. The application of extracellular LPA significantly increases the coefficient of APD(90) variability. LPA increased L-type calcium current (I(Ca,L)) density without altering its activation or deactivation properties. In contrast, LPA has no effect on two other ventricular repolarizing currents, the transient outward potassium current (I(to)) and the delayed rectifier potassium current (I(K)). In arterially perfused rabbit left ventricular wedge preparations, the monophasic action potential duration, QT interval, and Tpeak-end are prolonged by LPA. LPA treatment also significantly increases the incidence of ventricular tachycardia induced by S(1)S(2) stimulation. Notably, the effects of LPA on action potentials and I(Ca,L) are PTX-sensitive, suggesting LPA action requires a G(i)-type G protein. In conclusion, LPA prolongs APD and increases electrophysiological instability in isolated rabbit myocardial preparations by increasing I(Ca,L) in a G(i) protein-dependent manner.
authors.affiliation: Department of Cardiology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wei
authors.forename: Li-qun
authors.initials: LQ
authors.lastname: Zhao
authors.forename: Bao-zhen
authors.initials: BZ
authors.lastname: Qi
authors.forename: Xing
authors.initials: X
authors.lastname: Xiao
authors.forename: Li
authors.initials: L
authors.lastname: He
authors.forename: Gen-qing
authors.initials: GQ
authors.lastname: Zhou
authors.forename: Song-wen
authors.initials: SW
authors.lastname: Chen
authors.forename: Hong-li
authors.initials: HL
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Ruan
authors.forename: Cun-tai
authors.initials: CT
authors.lastname: Zhang
authors.forename: Shao-wen
authors.initials: SW
authors.lastname: Liu
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism* / Q000502:physiology; D020013:Calcium Signaling; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008246:Lysophospholipids / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin / Q000494:pharmacology; D011817:Rabbits; D016276:Ventricular Function / Q000187:drug effects
chemical_list: D020746:Calcium Channels, L-Type; D008246:Lysophospholipids; D037342:Pertussis Toxin; C032881:lysophosphatidic acid