| First Author | Lynch RM | Year | 2008 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 294 |
| Issue | 3 | Pages | H1407-16 |
| PubMed ID | 18192219 | Mgi Jnum | J:132410 |
| Mgi Id | MGI:3775896 | Doi | 10.1152/ajpheart.00855.2007 |
| Citation | Lynch RM, et al. (2008) Clearance of store-released Ca2+ by the Na+-Ca2+ exchanger is diminished in aortic smooth muscle from Na+-K+-ATPase {alpha}2-isoform gene-ablated mice. Am J Physiol Heart Circ Physiol 294(3):H1407-16 |
| abstractText | Two alpha-isoforms of the Na(+)-K(+)-ATPase are expressed in vascular smooth muscle cells (VSMCs). The alpha(1)-isoform is proposed to serve a cytosolic housekeeping role, whereas the alpha(2)-isoform modulates Ca(2+) storage via coupling to the Na(+)-Ca(2+) exchanger (NCX) in a subsarcolemmal compartment. To evaluate the ramifications of this proposed interaction, Ca(2+)-store load and the contributions of the primary Ca(2+) transporters to Ca(2+) clearance were studied in aortic VSMCs from embryonic wild-type (WT) and Na(+)-K(+)-ATPase alpha(2)-isoform gene-ablated, homozygous null knockout (alpha(2)-KO) mice. Ca(2+) stores were unloaded by inhibiting the sarco(endo)plasmic reticulum Ca(2+)-ATPase with cyclopiazonic acid (CPA) in Ca(2+)-free media to limit Ca(2+) influx. Ca(2+) clearance by the plasma membrane Ca(2+)-ATPase (PMCA), NCX, or mitochondria was selectively inhibited. In WT VSMCs, NCX accounted for 90% of the Ca(2+) efflux. In alpha(2)-KO VSMCs, preferential clearance of store-released Ca(2+) by NCX was lost, whereas PMCA activity was increased. Selective inhibition of the alpha(2)-isoform (0.5 muM ouabain for 20 min), before treatment with CPA enhanced the store load in VSMCs from WT, but not alpha(2)-KO mice. A subsequent analysis of capacitative Ca(2+) entry (CCE) indicated that the magnitude of Ca(2+) influx was significantly greater in alpha(2)-KO cells. Our findings support the concept of a subsarcolemmal space where the alpha(2)-isoform coupled with NCX modulates Ca(2+)-store function and, thereby, CCE. |
