Elevated intracellular Ca2+ affects Lii-Nao countertransport in human red blood cells.
Changes in cytoplasmic Ca2+ concentration and in Lii-Nao countertransport activity have been shown to be associated with essential hypertension. Elevated intracellular free [Ca2+], as well as abnormalities of Ca2+ binding and transport have been reported in cells from different tissues of hypertensive laboratory animals and essential hypertensive patients. Similarly, enhanced rates of Lii-Nao countertransport and the modified pattern of the temperature dependence of this activity in red blood cells from essential hypertensive patients have been previously demonstrated. The aim of the present study was to investigate possible interaction between changes in intracellular free [Ca2+] and the Lii-Nao exchange in human red blood cells. The ionophore ionomycin was used to allow Ca2+ incorporation into the cells in a dose-dependent manner. The elevation of intracellular [Ca2+], in turn, resulted in enhanced Li+ efflux from the cells. At 3 microM, ionomycin selectively and significantly enhanced the Lii-Nao countertransport but not Li+ leakage from the cells. EGTA totally abolished the effect of ionomycin, indicating that the effect is directly related to Ca2+. As low as 0.4 microM Ca2+ caused a statistically significant effect. The maximal effect of Ca2+ on the Lii-Nao countertransport was achieved around the external pH range of 6.8-7.5. In contrast, the leakage of Li+ was significantly enhanced by Ca2+ at a pH of 7.4 and above. Ca2+ did not affect the Km of the Lii-Nao countertransport for Li+. Amiloride, which inhibits Na+/H+ exchange, inhibited only 10% of the Ca2+-enhanced countertransport. It is concluded that Ca2+ may play a role in the regulation of Lii-Nao countertransport in erythrocytes.
Agam
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Department of Biology, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Hatzav
P
P
Abekasis
S
S
Loven
A
A
Livne
A
A
D017920:Antiporters; D002118:Calcium / Q000097:blood* / Q000502:physiology; D002352:Carrier Proteins / Q000097:blood*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D004987:Ethers / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D015759:Ionomycin; D007700:Kinetics; D008094:Lithium / Q000097:blood; D011188:Potassium / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D013816:Thermodynamics
D017920:Antiporters; D002352:Carrier Proteins; D004987:Ethers; C045885:sodium-lithium countertransporter; D015759:Ionomycin; D008094:Lithium; D012964:Sodium; D011188:Potassium; D002118:Calcium