S. Yamaguchi et al., SELECTIVE IMPAIRMENT OF HCO3--DEPENDENT PH(I) REGULATION BY LYSOPHOSPHATIDYLCHOLINE IN GUINEA-PIG VENTRICULAR MYOCARDIUM, Cardiovascular Research, 37(1), 1998, pp. 179-186
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.