Blaustein M P, Juhaszova M, Golovina V A
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201, USA.
Clin Exp Hypertens. 1998 Jul-Aug;20(5-6):691-703. doi: 10.3109/10641969809053247.
Arterial smooth muscle (ASM) contraction is triggered by agonist-evoked Ca2+ mobilization from sarcoplasmic reticulum (SR). The amount of Ca2+ released, and thus, the magnitude of the contractions, depends directly on SR Ca2+ content. Na+ pump inhibition by cardiotonic steroids (CTS) indirectly increases the Ca2+ content of the SR and, thus, contractility. This sequence of events does not, however, account for the multiple Na+ pump alpha subunit isoforms with different affinities for Na+ and for CTS, nor does it explain the cardiotonic and vasotonic effects of low doses of CTS that do not elevate cytosolic Na+ or Ca2+. We show that the Na+ pump high ouabain affinity (alpha3) isoform and the plasmalemmal (PM) Na/Ca exchanger are confined to PM domains that overlie junctional SR in ASM, while low ouabain affinity alpha1 and the PM Ca2+ pump are uniformly distributed in the PM. Thus, low doses of CTS, including an endogenous ouabain-like compound, influence cytosolic Na+ and (indirectly) Ca2+ concentrations only in the cytoplasmic clefts between the PM and junctional SR (a functional unit we call the "plasmerosome"). In turn, this modulates the Ca2+ content of the junctional SR and cell responsiveness.
动脉平滑肌（ASM）收缩由激动剂诱发的肌浆网（SR）释放Ca2+所触发。释放的Ca2+量，进而收缩的幅度，直接取决于SR的Ca2+含量。强心甾类化合物（CTS）抑制Na+泵可间接增加SR的Ca2+含量，从而增强收缩性。然而，这一系列事件并不能解释对Na+和CTS具有不同亲和力的多种Na+泵α亚基同工型，也无法解释低剂量CTS在不升高胞质Na+或Ca2+情况下的强心和血管收缩作用。我们发现，Na+泵高哇巴因亲和力（α3）同工型和质膜（PM）Na+/Ca2+交换体局限于ASM中位于连接肌浆网上方的质膜区域，而低哇巴因亲和力的α1和质膜Ca2+泵则均匀分布于质膜中。因此，低剂量的CTS，包括内源性类哇巴因化合物，仅在质膜与连接肌浆网之间的胞质裂隙（我们称之为“质膜小体”的功能单位）中影响胞质Na+和（间接）Ca2+浓度。反过来，这又调节了连接肌浆网的Ca2+含量和细胞反应性。
