Noël F, Wibo M, Godfraind T
Laboratoire de Pharmacologie, Université Catholique de Louvain, Brussels, Belgium.
Biochem Pharmacol. 1991 Jan 15;41(2):313-5. doi: 10.1016/0006-2952(91)90494-p.
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.
成年大鼠心室微粒体组分中的α1和α2（Na +，K +）-ATP酶同工型不能通过密度梯度离心分离。两种同工型主要在低密度亚组分中回收，其分布模式与其他典型质膜成分（5'-核苷酸酶、毒蕈碱受体）的分布模式重叠，但与主要与高密度亚组分相关的1,4-二氢吡啶受体的分布模式不同。因此，两种（Na +，K +）-ATP酶同工型基本上存在于非连接肌膜结构域，即在细胞表面，而1,4-二氢吡啶受体（电压依赖性钙通道）似乎更集中在主要起源于横管的连接结构域中。因此，低浓度哇巴因在大鼠心室中的高变力作用不能基于高亲和力受体（α2同工型）在连接结构附近的优先定位来解释。高、低浓度哇巴因变力作用的差异可能与α1和α2同工型相关的刺激反应偶联差异有关，低浓度作用对Na（+）-H +交换抑制剂乙基异丙基氨氯吡咪的更大敏感性表明了这一点。
