Erythrocyte membrane Ca2+-pumping ATPase of hypertensive humans: Reduced stimulation by calmodulin

Abstract

The Ca2+-pumping ATPase of erythrocyte plasma membranes of hypertensive humans (HTN) show, in the absence of calmodulin, a low Vmax comparable to that of the enzyme of the erythrocyte membranes of normotensive humans (NTN). Although the addition of calmodulin (1.5 μgper ml) increased the maximum activity of the calcium pump of membranes of HTN and NTN individuals by at least 2-fold and 4-fold, respectively, the activator protein partially purifed from the erythrocytes of HTN individuals enhanced the activity of the enzyme in a fashion similar to that of the protein obtained from the haemolysate of NTN individuals. A determination of the dependence of the activity of the pump on concentration of ATP revealed that the Km (ATP) of the enzyme of membranes of HTN individuals is 52% higher than that of the enzyme of membranes of NTN individuals, while the Vmax (1.75 ± 0.28 μmol ATP mg protein-1 h-1) of the pump is 46% lower in the membranes of HTN humans than that of the enzyme of membranes of normal individuals (3.25 ± 0.42 μmol ATP mg protein-1 h-1). It seems likely from these results that elevated erythrocyte Ca2+ concentration associated with essential hypertension may be due to a defective interaction between the Ca2+-pumping ATPase and the calmodulin Ca2+ complex,

Control of the erythrocyte free Ca2+ concentration in essential hypertension.

“…The basal activity was also found unchanged in EGTA-treated membranes, but its stimulation by calmodulin was reduced when compared with that of normotensive subjects. 12 - 16 Essential hypertension has been also reported to be associated with decreased 45 Ca 2+ uptake 17 and membrane Ca 2+ binding 1418 - 19 and increased or decreased total intracellular calcium content, measured by flame spectrometry or flameless atomic absorption. 20 - 21 Recently, the erythrocyte [Ca 2+ ]j, evaluated by nuclear magnetic resonance of a fluorinated derivative of quin-2 (2-[(2-bis[carboxymethyl]-amino-5-methylphenoxy)-methyl] -6 -methoxy-8 -bis [carboxymethyl] aminoquin-oline) or by fluorescence of fluo-3, was reported to be raised in hypertensive patients.…”