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Effect of platelet-activating factor (PAF) on sodium calcium exchange in cardiac sarcolemmal vesicles
H P Meng1, M J Kutryk, G N Pierce
1Division of Cardiovascular Sciences, St. Boniface General Hospital Research Center, Winnipeg, Canada.
Abstract:
The effects of platelet-activating factor (PAF) on Na(+)-dependent calcium uptake in myocardial sarcolemmal vesicles were examined in order to clarify its mechanism of inotropic action on the heart. PAF (40 and 20 microM) significantly inhibited Na(+)-Ca2+ exchange by 61% and 37%, respectively. Both initial rate of exchange and maximal exchange were inhibited. The Km for the reaction was not altered but Vmax was lowered 55% by PAF. Lyso-PAF inhibited Na(+)-Ca2+ exchange to a similar degree as PAF. CV-3988, a specific PAF receptor antagonist, failed to diminish the inhibitory effect of PAF on Na(+)-Ca2+ exchange, suggesting that the effect of PAF on Na(+)-Ca2+ exchange is not via a receptor mechanism. The passive permeability of sarcolemmal vesicles to Ca2+ was markedly elevated after PAF treatment. However, this effect could not account for the decrease in Na(+)-Ca2+ exchange. Interestingly, passive Ca2+ binding to cardiac sarcolemma was increased by 40 microM PAF. This study indicates that a depression of Na(+)-Ca2+ exchange probably does not play a role in the negative inotropic effect of PAF on the myocardium under physiological conditions. Its mechanism of action on Na(+)-Ca2+ exchange is discussed.
Insights
Platelet-activating factor (PAF) inhibits cardiac Na(+)-Ca2+ exchange, but this effect is not receptor-mediated. This inhibition likely does not contribute to PAF's negative inotropic action on the heart.
Area of Science:
- Cardiovascular Physiology
- Cellular Electrophysiology
- Pharmacology
Background:
- Platelet-activating factor (PAF) is implicated in cardiac function.
- Understanding PAF's mechanism of inotropic action requires investigating its effects on ion transport.
Purpose of the Study:
- To elucidate the mechanism by which PAF affects Na(+)-dependent calcium uptake in myocardial sarcolemmal vesicles.
- To determine if PAF's action on Na(+)-Ca2+ exchange is receptor-mediated.
Main Methods:
- Utilized myocardial sarcolemmal vesicles to study Na(+)-dependent calcium uptake.
- Assessed the effects of varying concentrations of PAF and Lyso-PAF on Na(+)-Ca2+ exchange kinetics.
- Investigated the role of PAF receptors using the antagonist CV-3988.
- Measured passive Ca2+ permeability and binding to cardiac sarcolemma.
Main Results:
- PAF significantly inhibited Na(+)-Ca2+ exchange in a dose-dependent manner.
- PAF reduced the Vmax of Na(+)-Ca2+ exchange without altering Km.
- The PAF receptor antagonist CV-3988 did not block PAF's inhibitory effect on Na(+)-Ca2+ exchange.
- PAF increased passive Ca2+ permeability and binding to cardiac sarcolemma.
Conclusions:
- PAF inhibits cardiac Na(+)-Ca2+ exchange through a non-receptor-mediated mechanism.
- The observed inhibition of Na(+)-Ca2+ exchange by PAF is unlikely to be the primary cause of its negative inotropic effect in physiological conditions.