Lysophosphatidylcholine, a metabolite which accumulates early in myocardium during ischemia, reduces gap junctional coupling in cardiac cells.
Lysophosphatidylcholine (LPC) is a metabolite that accumulates rapidly during cardiac ischemia in animal and human hearts. LPC induces electrophysiological changes including action potential alterations and cardiac arrhythmias. Since there is increasing evidence that disrupted cell coupling can contribute to the generation of cardiac arrhythmias under ischemic conditions, this study was designed to assess the effects of LPC on gap junction coupling between cardiac cell pairs using the dual whole-cell voltage-clamp technique. To measure gap junction resistance (r(j)), both cells of a pair were first clamped to a common holding potential and then, one cell was stepped to various voltages (20 mV steps from -50 to +50 mV). Junctional conductance (g(j)=1/r(j)) was derived from the junctional current recorded in the non-stimulated cell divided by the trans-junctional voltage. Extracellular medium was set to minimize non-junctional membrane conductance. LPC induced a decrease in g(j)after about 3, 8 and 12 min superfusion, respectively, for 50, 10 and 5 micromol/l. When LPC was continuously superfused (no washout), no steady-state was observed but a complete uncoupling (i.e. when the junctional resistance is infinitely high) after a delay of 7.3+/-1.2 min, 11.3+/-6.0 min, 15. 2+/-5.5 min and 23.3+/-6.0 min, respectively, for LPC 50 (n=5), 20 (n=4), 10 (n=5) and 5 (n=3) micromol/l. Mg(2+(out))at a concentration of 5 mmol/l exerted protective effects against LPC-induced uncoupling. In conclusion, LPC, at concentrations measured in situ during cardiac ischemia, is a potent inhibitor of gap junction communications between cardiac cells. Impaired junctional communications due to LPC accumulation early during ischemia could decrease electrical conduction and contribute to the genesis of malignant arrhythmias.
Daleau
P
P
Department of Medicine, Faculty of Medicine, Laval University and Quebec Heart Institute, Laval Hospital, Sainte-Foy, QC, Canada.
D000818:Animals; D002478:Cells, Cultured; D017629:Gap Junctions / Q000378:metabolism*; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D016276:Ventricular Function
D008244:Lysophosphatidylcholines