SELECTIVE IMPAIRMENT OF HCO3--DEPENDENT PH(I) REGULATION BY LYSOPHOSPHATIDYLCHOLINE IN GUINEA-PIG VENTRICULAR MYOCARDIUM

Objective: The aim was to examine the effects of lysophosphatidylcholi ne (LPC), an amphiphilic lipid metabolite in ischemic myocardium, on i ntracellular pH (pH(i)) regulatory systems in guinea pig papillary mus cles. Methods: In CO2/HCO3--buffered Tyrode solution, pH(i), intracell ular Na+ activity (a(Na)(i)) and membrane potential of isolated guinea pig papillary muscles were measured using ion-selective microelectrod e and conventional microelectrode. Standard ammonium prepulsing with 2 0 mM NH4Cl was used to produce an intracellular acid load, and effects of LPC on the pH i recovery from acidosis were evaluated in the absen ce and presence of a transport inhibitor. Results: LPC acidified the r esting pH(i) by 0.03 +/- 0.01 pH units (it = 15, P < 0.01) concomitant ly with a slight decrease in resting membrane potential and an increas e in a(Na)(i) in quiescent preparations. The pH(i) recovery rate from an intracellular acid load was decreased to 83 +/- 4% of the control v alue by 30 mu M LPC (n = 8, P < 0.05) but not by 30 mu M phosphatidylc holine (PC). In the presence of 10 mu M 5-(N,N-hexamethylene) amilorid e (HMA), a Na+-H+ exchange inhibitor, LPC still slowed pH(i) recovery from an intracellular acid load to 77 +/- 4% of the control (n = 5, P < 0.05). However, LPC failed to alter the pH(i) recovery rate in the p resence of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS, 0 .5 mM), a Na+-HCO3-; symport inhibitor. Conclusion: LPC impairs Na+-HC O3- symport but not Na+-H+ exchange, and LPC may potentiate its arrhyt hmogenic action by intensifying the intracellular acidosis in ischemic myocardium. (C) 1998 Elsevier Science B.V.