CARDIAC-HYPERTROPHY IN THE FERRET INCREASES EXPRESSION OF THE NA+-K+-ATPASE ALPHA(1)-ISOFORM BUT NOT ALPHA(3)-ISOFORM

Work overload alters expression of the Na+-K+-adenosinetriphosphatase (ATPase) multigene family in the myocardium. However, due to lack of an appropriate animal model, very little is known regarding regulation of the alpha(3)-isoform. We previously reported that adult ferret myocardium expresses the alpha(1)- and alpha(3)-isoforms of Na+-K+-ATPase. In the current study we examined the relative abundances of these isoforms in a recently developed ferret model of pressure-overload cardiac hypertrophy. Ferrets with abdominal aortic constriction (Coarc) developed significant left ventricular hypertrophy based on altered morphometric measurements and switching of the myosin heavy chain isoforms. Western and Northern blotting analyses showed that in hypertrophied left ventricles of Coarc ferrets the abundance of alpha(1)-protein increased (27%), whereas that of alpha(1)-mRNA remained unchanged. In nonhypertrophied right ventricles of Coarc ferrets abundance of alpha(1)-protein remained unchanged. Expression of the alpha(3)-isoform in left ventricles of Coarc ferrets remained unchanged at both protein and mRNA levels. By contrast, abundance of beta(1)-mRNA increased significantly (31%), whereas beta(1)-protein remained unchanged. Na+-K+-ATPase activity, estimated by K+-dependent nitrophenyl phosphatase activity, did not differ between left ventricular homogenates from Coarc and sham-operated ferrets. In conclusion, these studies indicate that in hypertrophied ferret heart Na+-K+-ATPase isoforms are differentially regulated at pretranslational, as well as at translational-posttranslational levels.