In this study, we determined the role of caveolae and the ionic mechanisms that mediate shear stress-mediated vasodilation (SSD). We found that both TRPV4 and SK channels are targeted to caveolae in freshly isolated bovine coronary endothelial cells (BCECs) and that TRPV4 and KCa2.3 (SK3) channels are co-immunoprecipitated by anti-caveolin-1 antibodies. Acute exposure of BCECs seeded in a capillary tube to 10 dynes/cm2 of SS resulted in activation of TRPV4 and SK currents. However, after incubation with HC067047 (TRPV4 inhibitor) SK currents could no longer be activated by SS, suggesting SK channel activation by SS was mediated through TRPV4. SK currents in BCECs were also activated by isoproterenol or by GSK1016790A (TRPV4 activator). In addition, pre-incubation of isolated coronary arterioles with apamin (SK inhibitor) resulted in a significant diminution of SSD while pre-incubation with HC067047 produced vasoconstriction by SS. Exposure of BCECs to SS (15 dynes/cm2 16 h) enhanced the production of nitric oxide and PGI2, and facilitated the translocation of TRPV4 to the caveolae. Inhibition of TRPV4 abolished the SS-mediated intracellular Ca2+ ([Ca2+]i) increase in BCECs. These results indicate a dynamic interaction in the vascular endothelium among caveolae, the TRPV4 and SK3 channels. This caveolae-TRPV4-SK3 channel complex underlies the molecular and ionic mechanisms that modulate SSD in the coronary circulation.
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Δευτέρα 18 Σεπτεμβρίου 2017
Role of the Endothelial Caveolae Microdomain in Shear Stress-Mediated Coronary Vasorelaxation [Molecular Biophysics]
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- Scholar : Ειδοποίηση Μελετητή - [ Εξωτε - 8/31/2017 - Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174,00302841026182
- Scholar : Ειδοποίηση Μελετητή - [ ΦΩΝΗΤ - 8/31/2017 - Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174,00302841026182
- Scholar : Ειδοποίηση Μελετητή - [ ΑΚΟΥΣ - 8/31/2017 - Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174,00302841026182
- Scholar : Ειδοποίηση Μελετητή - [ ωτα ] - 8/31/2017 - Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174,00302841026182
- Scholar : Ειδοποίηση Μελετητή - [ ΑΚΟΗ ] - 8/31/2017 - Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00306932607174,00302841026182
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