| Autor: |
Eun A. Ko, Jun Wan, Yamamura, Aya, Zimnicka, Adriana M., Yamamura, Hisao, Hae Young Yoo, Tang, Haiyang, Smith, Kimberly A., Sundivakkam, Premanand C., Zeifman, Amy, Ayon, Ramon J., Makino, Ayako, Yuan, Jason X.-J. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Cell Physiology; Jun2013, Vol. 304 Issue 11, pC1042-C1052, 11p |
| Abstrakt: |
Electromechanical coupling via membrane depolarization-mediated activation of voltagedependent Ca2+ channels (VDCC) is an important mechanism in regulating pulmonary vascular tone, while mouse is an animal model often used to study pathogenic mechanisms of pulmonary vascular disease. The function of VDCC in mouse pulmonary artery (PA) smooth muscle cells (PASMC), however, has not been characterized, and their functional role in reactive oxygen species (ROS)-mediated regulation of vascular function remains unclear. In this study, we characterized the electrophysiological and pharmacological properties of VDCC in PASMC and the divergent effects of ROS produced by xanthine oxidase (XO) and hypoxanthine (HX) on VDCC in PA and mesenteric artery (MA). Our data show that removal of extracellular 2+ or application of nifedipine, a dihydropyridine VDCC blocker, both significantly inhibited 80 mM K+-mediated PA contraction. In freshly dissociated PASMC, the maximum inward 2+ currents were -2.6 ± 0.2 pA/pF at +10 mV (with a holding potential of -70 mV). Window currents were between -40 and +10 mV with a peak at -15.4 mV. Nifedipine inhibited currents with an IC50 of 0.023 μM, and 1 μM Bay K8644, a dihydropyridine VDCC agonist, increased the inward currents by 61%. XO/HX attenuated 60 mM K+-mediated increase in cytosolic free 2+ concentration ([Ca2+]cyt) due to 2+ influx through VDCC in PASMC. Exposure to XO/HX caused relaxation in PA preconstricted by 80 mM K+ but not in aorta and MA. In contrast, H2O2 inhibited high K+-mediated increase in [2+]cyt and caused relaxation in both PA and MA. Indeed, RT-PCR and Western blot analysis revealed significantly lower expression of CaV1.3 in MA compared with PA. Thus our study characterized the properties of VDCC and demonstrates that ROS differentially regulate vascular contraction by regulating VDCC in PA and systemic arteries. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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