A study of the interaction between the Na+, K+ pump and Na+:Ca2+ exchange in macrophages and vascular smooth muscle cells.
Blaustein (Am J Physiol 1977;232:C165-C173) postulated that Na+:Ca2+ exchange in vascular smooth muscle plays a key role in the link between sodium and hypertension. Investigation of this hypothesis was facilitated by the use of: a) Sr2+, a slowly transported Ca2+ analogue, and b) new quasispecific inhibitors of Na+:Ca2+ exchange such as 2',4'-dimethylbenzamil. Preliminary experiments in mouse macrophages showed that the initial rate of Sr2+ uptake lasted for at least 15 minutes and was therefore easier to measure than the initial rate of unidirectional isotopic Ca2+ influx (which lasted less than 30 seconds). In cells with normal Na+ content, basal Sr2+ influx (432 +/- 77 mumol [L cells X h]-1; mean +/- SEM of seven experiments) exhibited properties compatible with a ground membrane leak for divalent cations (quasilinear dependence on the external Sr2+ concentration, partial or full resistance to external Ca2+, Ba2+, verapamil, and 2',4'-dimethylbenzamil). Membrane depolarization by external K+ was unable to modify basal Sr2+ uptake. Conversely, a 100% increase in cell Na+ content by preincubation with ouabain increased the rate of Sr2+ uptake by 233 +/- 48 mumol (L cells X h)-1 (mean +/- SEM of seven experiments). 2',4'-Dimethylbenzamil, but not the Ca2+ antagonists diltiazem or methoxyverapamil, inhibited ouabain-stimulated Sr2+ influx (IC50 of about 3 X 10(-5) M). 2',4'-Dimethylbenzamil was also able to inhibit Na+ efflux (by 3.05 +/- 0.98 mmol (L cells X h)-1; mean +/- SEM of three experiments) suggesting the existence of Na+:Sr2+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)
Galli
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C
INSERM U7, Hôpital Necker, Paris, France.
Hannaert
P
P
Diaz
A S
AS
Cragoe
E
E
Garay
R
R
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger; D013324:Strontium / Q000378:metabolism
D002352:Carrier Proteins; D007473:Ion Channels; D019831:Sodium-Calcium Exchanger; C053494:2',4'-dimethylbenzamil; D010042:Ouabain; D000584:Amiloride; D012964:Sodium; D011188:Potassium; D013324:Strontium