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 func tion of secondary active transporters, and for osmoregulation of the cell. Since inhibition of the enzyme by cardiac glycosides results in increased c ontractility of the heart muscle and increased blood pressure, we were inte rested in whether there is a correlation between hypertension and expressio n of the various isoforms of the sodium pump. In addition, we also examined the expression of the isoforms of the sarcoplasmic and plasma membrane Ca2 +-ATPase, the Na+/Ca2+- and Na+/H+-exchangers, and Na+ channel and Ca2+ cha nnel isoforms. Total mRNA was isolated from 50 mg tissue from the right atr ium of hypertensive and normotensive patients who were undergoing cardiac s urgery. After reverse transcription and subsequent amplification of ion tra nsporter-specific cDNA fragments by polymerase chain reaction (PCR) in the presence of [alpha-P-32]dCTP, quantification of the amplified fragments was carried out by the Phosphorimager technique. The data obtained show that t he al subunit mRNA is expressed similarly in normotensive and hypertensive patients. The amount of alpha2 subunit mRNA, however, is increased 5-fold i n hypertensive patients. In the same group, the amount of alpha3 isoform is also significantly increased, although not as dramatically as the alpha2 i soform. Besides the Na+,K+-ATPase isoforms, a significant increase in the e xpression of mRNA for the Na+/Ca2+-exchanger and the plasma membrane Ca2+-A TPase isoforms was detected. It is possible that the observed changes in mR NA expression for these ion transporters reflect compensatory mechanisms to overcome a defective Na+ and Ca2+ metabolism in the tissues of hypertensiv e patients or reflect defects directly involved in the cause of hypertensio n. The expression of mRNA for all other transporters investigated was unalt ered. (C) 2001 Elsevier Science BN. All rights reserved.