Role of the Na + pump in smooth muscle contractile regulation

Abstract

The last 20 years have seen substantial biochemical and pharmacological characterization of Na +/K +-ATPase in various mammalian tissues, but its study in vascular smooth muscle has lagged behind. In this review, Julius Allen and Stephen Navran describe recent developments in the study of the Na + pump in this issue and highlight important differences in its activity and control. It has been shown that despite the existence of fewer pump sites in smooth muscle when compared to cardiac muscle, the 86Rb uptake rate of the tissue types are comparable, suggesting different modes of pump regulation. The fewer pump sites also provide rationale for lower observable Na +/K +-ATPase activity. Data clearly suggest that the Na + pump in vascular smooth muscle can also be activated in two ways: (1) directly by the occupation of the cationic activation binding sites and (2) indirectly by modulation of the pump by agonists (‘energized pump’) so that pump sensitivity to cationic activation is altered. Such an hypothesis is supported by differences in K +-induced relaxation of canine renal and femoral arteries, and norepinephrine and forskolin stimulation of 86Rb uptake by the renal artery and not the femoral. These data suggest that the Na + pump plays an important role in regulation of smooth muscle contractility, and may well play an important role in determination of smooth muscle contractile heterogeneity.