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Int J Biol Sci 2017; 13(10):1242-1253. doi:10.7150/ijbs.21475

Research Paper

Distinct Effects of Ca2+ Sparks on Cerebral Artery and Airway Smooth Muscle Cell Tone in Mice and Humans

Qing-Yang Zhao1*, Yong-Bo Peng1*, Xiao-Jing Luo1*#, Xi Luo1*, Hao Xu1*, Ming-Yu Wei1*, Qiu-Ju Jiang1, Wen-Er Li1#, Li-Qun Ma1, Jin-Chao Xu1, Xiao-Cao Liu1, Dun-An Zang1, Yu-San She1, He Zhu1, Jinhua Shen1, Ping Zhao1, Lu Xue1, Meng-Fei Yu1, Weiwei Chen1, Ping Zhang2, Xiangning Fu3, Jingyu Chen4, Xiaowei Nie4, Chenyou Shen4, Shu Chen5, Shanshan Chen5, Jingcao Chen6, Sheng Hu7, Chunbin Zou8, Gangjian Qin9, Ying Fang10, Jiuping Ding10, Guangju Ji11, Yun-Min Zheng12, Tengyao Song12, Yong-Xiao Wang12, Qing-Hua Liu1✉

1. Institute for Medical Biology and Hubei Provincial Key Laboratory for Protection and Application of Special Plants in Wuling Area of China, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China;
2. Department of Cerebral Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430032, Hubei, China;
3. Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430032, Hubei, China;
4. Wuxi &Jiangsu Key Laboratory of Organ Transplantation, Department of Cardiothoracic Surgery, Lung Transplant Group, Wuxi People's Hospital, Nanjing Medical University, Jiangsu, China;
5. Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430032, Hubei, China;
6. Department of Cerebral Surgery, Zhongnan Hospital, Wuhan University Medical College, Wuhan, 430071, Hubei, China;
7. Department of Medical Oncology, Hubei Cancer Hospital, Wuhan, 430079, Hubei, China;
8. Acute Lung Injury Center of Excellence, Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA;
9. Department of Biomedical Engineering, School of Medicine & School of Engineering, University of Alabama Birmingham, AL, 35294, USA;
10. Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China;
11. National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China;
12. Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, 12208, USA.
* Q-Y Z., Y-B P., X-J L., X L., H X., M-Y W. contributed equally to this work.
# Current address: Institute of Pharmacology, University of Technology Dresden, Dresden 01307, Germany.

Abstract

The effects of Ca2+ sparks on cerebral artery smooth muscle cells (CASMCs) and airway smooth muscle cells (ASMCs) tone, as well as the underlying mechanisms, are not clear. In this investigation, we elucidated the underlying mechanisms of the distinct effects of Ca2+ sparks on cerebral artery smooth muscle cells (CASMCs) and airway smooth muscle cells (ASMCs) tone. In CASMCs, owing to the functional loss of Ca2+-activated Cl- (Clca) channels, Ca2+ sparks activated large-conductance Ca2+-activated K+ channels (BKs), resulting in a decreases in tone against a spontaneous depolarization-caused high tone in the resting state. In ASMCs, Ca2+ sparks induced relaxation through BKs and contraction via Clca channels. However, the integrated result was contraction because Ca2+ sparks activated BKs prior to Clca channels and Clca channels-induced depolarization was larger than BKs-caused hyperpolarization. However, the effects of Ca2+ sparks on both cell types were determined by L-type voltage-dependent Ca2+ channels (LVDCCs). In addition, compared with ASMCs, CASMCs had great and higher amplitude Ca2+ sparks, a higher density of BKs, and higher Ca2+ and voltage sensitivity of BKs. These differences enhanced the ability of Ca2+ sparks to decrease CASMC and to increase ASMC tone. The higher Ca2+ and voltage sensitivity of BKs in CASMCs than ASMCs were determined by the β1 subunits. Moreover, Ca2+ sparks showed the similar effects on human CASMC and ASMC tone. In conclusions, Ca2+ sparks decrease CASMC tone and increase ASMC tone, mediated by BKs and Clca channels, respectively, and finally determined by LVDCCs.

Keywords: Smooth muscle cells, Ca2+ sparks, BK channels, Ca2+-activated Cl- channels, L-type voltage-dependent Ca2+ channels.

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How to cite this article:
Zhao QY, Peng YB, Luo XJ, Luo X, Xu H, Wei MY, Jiang QJ, Li WE, Ma LQ, Xu JC, Liu XC, Zang DA, She YS, Zhu H, Shen J, Zhao P, Xue L, Yu MF, Chen W, Zhang P, Fu X, Chen J, Nie X, Shen C, Chen S, Chen S, Chen J, Hu S, Zou C, Qin G, Fang Y, Ding J, Ji G, Zheng YM, Song T, Wang YX, Liu QH. Distinct Effects of Ca2+ Sparks on Cerebral Artery and Airway Smooth Muscle Cell Tone in Mice and Humans. Int J Biol Sci 2017; 13(10):1242-1253. doi:10.7150/ijbs.21475. Available from http://www.ijbs.com/v13p1242.htm