Int J Biol Sci 2017; 13(10):1242-1253. doi:10.7150/ijbs.21475
Distinct Effects of Ca2+ Sparks on Cerebral Artery and Airway Smooth Muscle Cell Tone in Mice and Humans
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;
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