Abstract
Effects of membrane phospholipids on Na+-Ca2+ exchange and Na+ channel currents were studied in giant excised cardiac sarcolemmal patches. Phospholipids were suspended in an inert vehicle of α-tocopherol acetate and hexane and were then directly applied to the side of patch electrodes at a short distance from the tip during current recording. Phosphatidylserine strongly stimulated outward Na+-Ca2+ exchange current and altered the kinetics of cytoplasmic Na+- and Ca2+-dependent secondary modulation. This effect was partially reversed by phosphatidylcholine. Prolonged treatment with phosphatidylserine eliminated the inactivation transient normally observed upon rapid application of cytoplasmic Na+ but left cytoplasmic Ca2+ dependence largely intact. In such cases, subsequent chymotrypsin treatment removed cytoplasmic Ca2+ dependence, but had no further stimulatory effect, indicating maximum alleviation of inactivation by phosphatidylserine. While these results indicate that phosphatidylserine acts on a cytoplasmic, protease-sensitive regulatory domain of the exchanger, phosphatidylserine also stimulated the exchange current after deregulation by chymotrypsin, indicating an effect on the exchange mechanism itself. As in other myocyte preparations, cardiac Na+ currents in giant patches undergo a time-dependent negative shift in the voltage dependence of steady-state inactivation. Loss of phosphatidylserine from the cytoplasmic leaflet (i.e. loss of transbilayer asymmetry of phosphatidylserine distribution) does not appear to be the underlying cause, since phosphatidylserine did not reverse this shift, despite stimulation of Na+-Ca2+ exchange current in the same patches.
Original language | English (US) |
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Pages (from-to) | 347-355 |
Number of pages | 9 |
Journal | Pflügers Archiv European Journal of Physiology |
Volume | 423 |
Issue number | 5-6 |
DOIs | |
State | Published - Jun 1993 |
Keywords
- Heart
- Patch clamp
- Phosphatidylcholine
- Phosphatidylserine
- Sarcolemma
- Sodium channels
- Sodium-calcium exchange
ASJC Scopus subject areas
- Physiology
- Clinical Biochemistry
- Physiology (medical)