Expression of sodium pump isoforms and other sodium or calcium ion transporters in the heart of hypertensive patients.
The sodium pump (Na(+),K(+)-ATPase; EC 3.6.1.37) of animal cell membranes is the enzyme responsible for the maintenance of membrane potential, for the function of secondary active transporters, and for osmoregulation of the cell. Since inhibition of the enzyme by cardiac glycosides results in increased contractility of the heart muscle and increased blood pressure, we were interested in whether there is a correlation between hypertension and expression of the various isoforms of the sodium pump. In addition, we also examined the expression of the isoforms of the sarcoplasmic and plasma membrane Ca(2+)-ATPase, the Na(+)/Ca(2+)- and Na(+)/H(+)-exchangers, and Na(+) channel and Ca(2+) channel isoforms. Total mRNA was isolated from 50 mg tissue from the right atrium of hypertensive and normotensive patients who were undergoing cardiac surgery. After reverse transcription and subsequent amplification of ion transporter-specific cDNA fragments by polymerase chain reaction (PCR) in the presence of [alpha-(32)P]dCTP, quantification of the amplified fragments was carried out by the Phosphorimager technique. The data obtained show that the alphal subunit mRNA is expressed similarly in normotensive and hypertensive patients. The amount of alpha2 subunit mRNA, however, is increased 5-fold in hypertensive patients. In the same group, the amount of alpha3 isoform is also significantly increased, although not as dramatically as the alpha2 isoform. Besides the Na(+),K(+)-ATPase isoforms, a significant increase in the expression of mRNA for the Na(+)/Ca(2+)-exchanger and the plasma membrane Ca(2+)-ATPase isoforms was detected. It is possible that the observed changes in mRNA expression for these ion transporters reflect compensatory mechanisms to overcome a defective Na(+) and Ca(2+) metabolism in the tissues of hypertensive patients or reflect defects directly involved in the cause of hypertension. The expression of mRNA for all other transporters investigated was unaltered.
Jäger
H
H
Institut für Biochemie und Endokrinologie, Justus-Liebig-Universität Giessen, Fachbereich Veterinärmedizin, Frankfurter Strasse 100, D-35392 Giessen, Germany.
Wozniak
G
G
Akintürk
I H
IH
Hehrlein
F W
FW
Scheiner-Bobis
G
G
D000328:Adult; D000368:Aged; D000818:Animals; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis* / Q000235:genetics; D002462:Cell Membrane / Q000201:enzymology; D005260:Female; D006325:Heart Atria; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000378:metabolism; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms / Q000096:biosynthesis; D012333:RNA, Messenger / Q000302:isolation & purification; D017923:Sodium-Hydrogen Exchangers / Q000096:biosynthesis; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis* / Q000235:genetics
D020033:Protein Isoforms; D012333:RNA, Messenger; D017923:Sodium-Hydrogen Exchangers; D010042:Ouabain; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase