Effect of cholesterol and dipalmitoyl phosphatidylcholine enrichment on the kinetics of Na−Li exchange of human erythrocytes

Abstract

The effects of cholesterol loading and depletion and of a 10% replacement of native phosphatidylcholine by dipalmitoyl phosphatidylcholine (di 16:0-PC) on kinetic properties of human red cell Na-Li exchange have been studied. Compared to control erythrocytes (cholesterol/phospholipid ratio (C/P = 0.8-0.9], Vmax of phloretin-sensitive Li uptake and of Li efflux stimulated by extracellular Na (Nao) were reduced by 15-30% in cholesterol-loaded red cells (C/P = 1.05-1.33). The apparent Km values for external Li (Lio) and for internal Li (Lii) were decreased by about one-third in these cells. Cholesterol depletion (C/P = 0.7) exerted opposite effects on the kinetics of Nao-dependent Li efflux. On augmenting C/P from 0.66 to 1.0, Vmax of Nao-dependent Li efflux was reduced by about 30%; increasing C/P above 1.0 caused no further lowering of Vmax.Li leakage rates monotonically decreased over the whole range of C/P ratios examined (0.66-1.3). This indicates that Na-Li exchange and Li leak are differentially affected by cholesterol. Incorporation of di 16:0-PC (replacement of 3% of total red cell phospholipids) caused similar kinetic alterations of Na-Li exchange as a rise in membrane cholesterol by 20-50%. Notably, selective incorporation of di 16:0-PC into the outer monolayer increased both intra- and extracellular Li binding affinities of Na-Li exchange and lowered its maximum velocity. Thus, both di 16:0-PC enrichment and cholesterol loading exerted an uncompetitive type of transport inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased Na + -H + exchanger activity in the ileal brush-border membrane of spontaneously hypertensive rats

“…Therefore, it is reasonable to postulate that the NHE3 isoform is the one present in our BBMV preparations, with the same isoform present in the two vesicle populations. Membrane lipid composition and fluidity are also known to affect membrane-bound transport proteins [9,29], including the Na + /H + exchanger [30,31]. Previous studies in our lab have shown an increased membrane fluidity together with an enhancement in the ratio of cholesterol/phospholipid in the brush-border membrane from SHR, compared to WKY rats [32].…”

Alterations in heart and kidney membrane phospholipids in hypertension as observed by 31P nuclear magnetic resonance

“…For example, Lijnen et al (25) reported a significant correlation between total phospholipid content of erythrocyte membranes and the activities of Na + -Li + exchange, Na + -K + cotransport, and Na + pump. Engelmann et al (26,27) reported that a change in composition of only 3% of total membrane lipids could cause up to 40% variation in sodium-lithium countertransport activity. They also showed that small changes in membrane PC or Sph (~5% of total phospholipid) resulted in doubling or halving of the rate of Na + -Li + exchange (28).…”

“…To our knowledge, this study is the first report in the literature on alterations in phospholipids of the hypertensive heart and kidney, the two organs well known to be adversely affected in essential hypertension. It appears possible that these abnormalities may at least in part account for abnormal ion balance and ion transport observed in hypertensive heart and kidney cells (25)(26)(27)(28)51,52,55,(61)(62)(63)(64)(65)(66)(67)(68)(69)(70).…”