| Autor: |
Jin Zhang, Ren, Chongyu, Ling Chen, Navedo, Manuel F., Antos, Laura K., Kinsey, Stephen P., Iwamoto, Takahiro, Philipson, Kenneth D., Kotlikoff, Michael I., Santana, Luis F., Wier, W. Gil, Matteson, Donald R., Blaustein, Mordecai P. |
| Předmět: |
|
| Zdroj: |
American Journal of Physiology: Heart & Circulatory Physiology; May2010, Vol. 298 Issue 5, p1472-1483, 12p |
| Abstrakt: |
Mice with smooth muscle (SM)-specific knockout of Na+/Ca2+ exchanger type-1 (NCX1SM-/-) and the NCX inhibitor, SEA0400, were used to study the physiological role of NCX1 in mouse mesenteric arteries. NCX1 protein expression was greatly reduced in arteries from NCX1SM-/- mice generated with Cre recombinase. Mean blood pressure (BP) was 6-10 mmHg lower in NCX1SM-/- mice than in wild-type (WT) controls. Vasoconstriction was studied in isolated, pressurized mesenteric small arteries from WT and NCX1SM-/- mice and in heterozygotes with a global null mutation (NCX1Fx/-). Reduced NCX1 activity was manifested by a marked attenuation of responses to low extracellular Na+ concentration, nanomolar ouabain, and SEA0400. Myogenic tone (MT, 70 mmHg) was reduced by ∼15% in NCX1SM-/- arteries and, to a similar extent, by SEA0400 in WT arteries. MT was normal in arteries from NCX1Fx/- mice, which had normal BP. Vasoconstrictions to phenylephrine and elevated extracellular K+ concentration were significantly reduced in NCX1SM-/- arteries. Because a high extracellular K+ concentration-induced vasoconstriction involves the activation of L-type voltage-gated Ca2+ channels (LVGCs), we measured LVGC-mediated currents and Ca2+ sparkiets in isolated mesenteric artery myocytes. Both the currents and the sparklets were significantly reduced in NCX1SM-/- (vs. WT or NCX1Fx/-) myocytes, but the voltage-dependent inactivation of LVGCs was not augmented. An acute application of SEA0400 in WT myocytes had no effect on LVGC current. The LVGC agonist, Bay K 8644, eliminated the differences in LVGC currents and Ca2+ sparklets between NCX1SM-/- and control myocytes, suggesting that LVGC expression was normal in NCX1SM-/- myocytes. Bay K 8644 did not, however, eliminate the difference in myogenic constriction between WT and NCX 15M' arteries. We conclude that, under physiological conditions, NCX1-mediated Ca2+ entry contributes significantly to the maintenance of MT. In NCX1SM-/- mouse artery myocytes, the reduced Ca2+ entry via NCX1 may lower cytosolic Ca2+ concentration and thereby reduce MT and BP. The reduced LVGC activity may be the consequence of a low cytosolic Ca2+ concentration. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
