Jason X-J Yuan

Publications (171) View all

• Article: Functional Characterization of Voltage-dependent Ca2+ Channels in Mouse Pulmonary Arterial Smooth Muscle Cells: Divergent Effect of ROS.

  Eun A Ko, Jun Wan, Aya Yamamura, Adriana M Zimnicka, Hisao Yamamura, Hae Young Yoo, Haiyang Tang, Kimberly A Smith, Premanand C Sundivakkam, Amy Zeifman, Ramon J Ayon, Ayako Makino, Jason X-J Yuan
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  ABSTRACT: Electromechanical coupling via membrane depolarization-mediated activation of voltage-dependent Ca(2+) 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 Ca(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 Ca(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 [Ca(2+)]cyt due to Ca(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, H(2)O(2) inhibited high K(+)-mediated increase in [Ca(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 to PA. Thus, our study characterized the properties of VDCC and demonstrates that ROS differentially regulate vascular contraction by regulating VDCC in pulmonary and systemic arteries.
  AJP Cell Physiology 02/2013; · 3.54 Impact Factor
• Article: Human Models for Smooth Muscle Cell Differentiation.

  Amy L Firth, Jason X-J Yuan
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  ABSTRACT: NA.
  AJP Cell Physiology 01/2013; · 3.54 Impact Factor
• Article: Dihydropyridine Ca2+ Channel Blockers Increase Cytosolic [Ca2+] by Activating Ca2+-sensing Receptors in Pulmonary Arterial Smooth Muscle Cells.

  Aya Yamamura, Hisao Yamamura, Qiang Guo, Adriana M Zimnicka, Jun Wang, Eun A Ko, Kimberly A Smith, Nicole M Pohl, Shanshan Song, Amy Zeifman, Ayako Makino, Jason X J Yuan
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  ABSTRACT: Rationale: An increase in cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)) in pulmonary arterial smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction and an important stimulus for PASMC proliferation and pulmonary vascular remodeling. The dihydropyridine Ca(2+) channel blockers, such as nifedipine, have been used for treatment of idiopathic pulmonary arterial hypertension (IPAH). Objective: Our previous study demonstrated that the Ca(2+)-sensing receptor (CaSR) was upregulated and the extracellular Ca(2+)-induced increase in [Ca(2+)](cyt) was enhanced in PASMC from patients with IPAH and animals with experimental pulmonary hypertension. Here, we report that the dihydropyridines (e.g., nifedipine) increase [Ca(2+)](cyt) by activating CaSR in PASMC from IPAH patients (in which CaSR is upregulated), but not in normal PASMC. Methods and Results: The nifedipine-mediated increase in [Ca(2+)](cyt) in IPAH-PASMC was concentration dependent with an EC(50) of 0.20 µM. Knockdown of CaSR with siRNA in IPAH-PASMC significantly inhibited the nifedipine-induced increase in [Ca(2+)](cyt), whereas overexpression of CaSR in normal PASMC conferred the nifedipine-induced rise in [Ca(2+)](cyt). Other dihydropyridines, nicardipine and Bay K8644, had similar augmenting effects on the CaSR-mediated increase in [Ca(2+)](cyt) in IPAH-PASMC; however, the non-dihydropyridine blockers, such as diltiazem and verapamil, had no effect on the CaSR-mediated rise in [Ca(2+)](cyt). Conclusions: The dihydropyridine derivatives increase [Ca(2+)](cyt) by potentiating the activity of CaSR in PASMC independently of their blocking (or activating) effect on Ca(2+) channels; therefore, it is possible that use the dihydropyridine Ca(2+) channel blockers (e.g., nifedipine) to treat IPAH patients with upregulated CaSR in PASMC may exacerbate pulmonary hypertension.
  Circulation Research 01/2013; · 9.49 Impact Factor
• Article: Readership: The heart of Pulmonary Circulation.

  Jason X J Yuan, Nicholas W Morrell, Christina Holt, Ghazwan Butrous
  Pulmonary circulation. 01/2013; 3(1):1-2.
• Article: H2S, a gasotransmitter for oxygen sensing in carotid body Focus on "Endogenous H2S is required for Hypoxic Sensing by Carotid Body Glomus Cells"

  Kimberly A Smith, Jason X-J Yuan
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  ABSTRACT: No abstract.
  AJP Cell Physiology 09/2012; · 3.54 Impact Factor