18 research outputs found
Immunologic identification of Na+, K+ -ATPase isoforms in myocardium. Isoform change in deoxycorticosterone-acetate-salt hypertension
There are three isoforms of the catalytic (alpha) subunit of the Na+,K(+)-ATPase, each derived from a different gene, that differ in their sensitivity to inhibition by cardiac glycosides. Antibodies specific for the three isoforms were used to study Na+,K(+)-ATPase isoform expression in ventricular myocardium, where an understanding of digitalis receptor diversity is most important. In the rat heart, there is simultaneous expression of two isoforms in adult ventricle, and immunofluorescence studies demonstrated that both isoforms are expressed uniformly in cardiomyocytes. Hypertension and hypertrophy have been reported to selectively depress alpha 2 isoform mRNA levels, and we show in the present study that alpha 2 protein levels were correspondingly depressed in rats made hypertensive by uninephrectomy and treatment with deoxycorticosterone acetate and a high-salt diet. In the human heart, where mRNA for all three alpha isoforms has been reported, we detected all three isoform proteins (alpha 1, alpha 2, and alpha 3). Two isoforms (alpha 1 and alpha 3) predominated in the macaque heart; dissection of the heart showed uniformity of isoform expression in different ventricular regions but markedly less alpha 3 in the atrium. Finally, isoform-specific antibodies were used to detect which alpha isoforms were expressed in the ventricles of several commonly used experimental animals to test the correlation of isoform expression with cardiac glycoside-response heterogeneity. Two isoforms (alpha 1 and alpha 3) were found in canine myocardium, whereas only one (alpha 1) was found in sheep and guinea pig. Expression of Na+,K(+)-ATPase isoforms can thus be readily followed and related to the physiology of the digitalis receptor
Identification of a Cytoskeleton-bound Form of Phospholemman with Unique C-Terminal Immunoreactivity
Distinct neurological disorders with ATP1A3 mutations
Mechanisms of disease, diagnostics and therap
Distinct neurological disorders with ATP1A3 mutations.
Genetic research has shown that mutations that modify the protein-coding sequence of ATP1A3, the gene encoding the \u3b13 subunit of Na+/K+-ATPase, cause both rapid-onset dystonia parkinsonism and alternating hemiplegia of childhood. These discoveries link two clinically distinct neurological diseases to the same gene, however, ATP1A3 mutations are, with one exception, disease-specific. Although the exact mechanism of how these mutations lead to disease is still unknown, much knowledge has been gained about functional consequences of ATP1A3 mutations using a range of in-vitro and animal model systems, and the role of Na+/K+-ATPases in the brain. Researchers and clinicians are attempting to further characterise neurological manifestations associated with mutations in ATP1A3, and to build on the existing molecular knowledge to understand how specific mutations can lead to different diseases