Distribution of alpha 1 and alpha 2 (Na+,K+)-ATPase isoforms between the junctional (t-tubular) and non-junctional sarcolemmal domains of rat ventricle.
The alpha 1 and alpha 2 (Na+,K+)-ATPase isoforms in microsomal fractions from adult rat ventricle could not be separated by density gradient centrifugation. Both isoforms were mainly recovered in low-density subfractions and their distribution pattern was superimposable to those of other typical plasma membrane constituents (5'-nucleotidase, muscarinic receptors) but differed from that of 1,4-dihydropyridine receptors, which were mainly associated with high-density subfractions. Thus, both (Na+,K+)-ATPase isoforms were present essentially in the non-junctional sarcolemmal domain, i.e. at the cell surface, while 1,4-dihydropyridine receptors (voltage-dependent calcium channels) seemed much more concentrated in the junctional domain, which is predominantly of t-tubular origin. Therefore, the high inotropic efficacy of low ouabain concentrations in rat ventricle cannot be explained on the basis of a preferential localization of the high-affinity receptors (alpha 2 isoform) in the vicinity of junctional structures. The difference in inotropic efficacy between high and low ouabain concentrations might be related to differences in stimulus response coupling associated with alpha 1 and alpha 2 isoforms, as suggested by the greater sensitivity of the effect of low concentrations to ethylisopropylamiloride, an inhibitor of Na(+)-H+ exchange.
Noël
F
F
Laboratoire de Pharmacologie, Université Catholique de Louvain, Brussels, Belgium.
Wibo
M
M
Godfraind
T
T
D015720:5'-Nucleotidase / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002458:Cell Fractionation; D004095:Dihydropyridines / Q000378:metabolism; D006352:Heart Ventricles / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism*; D008861:Microsomes / Q000201:enzymology; D010042:Ouabain / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D012508:Sarcolemma / Q000201:enzymology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D004095:Dihydropyridines; D007527:Isoenzymes; D010042:Ouabain; D011813:Quinuclidinyl Benzilate; C038806:1,4-dihydropyridine; D015720:5'-Nucleotidase; D000254:Sodium-Potassium-Exchanging ATPase