Dataset Information

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

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 ?1 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.

SUBMITTER: Zhao QY

PROVIDER: S-EPMC5666523 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Zhao Qing-Yang QY Peng Yong-Bo YB Luo Xiao-Jing XJ Luo Xi X Xu Hao H Wei Ming-Yu MY Jiang Qiu-Ju QJ Li Wen-Er WE Ma Li-Qun LQ Xu Jin-Chao JC Liu Xiao-Cao XC Zang Dun-An DA She Yu-San YS Zhu He H Shen Jinhua J Zhao Ping P Xue Lu L Yu Meng-Fei MF Chen Weiwei W Zhang Ping P Fu Xiangning X Chen Jingyu J Nie Xiaowei X Shen Chenyou C Chen Shu S Chen Shanshan S Chen Jingcao J Hu Sheng S Zou Chunbin C Qin Gangjian G Fang Ying Y Ding Jiuping J Ji Guangju G Zheng Yun-Min YM Song Tengyao T Wang Yong-Xiao YX Liu Qing-Hua QH

International journal of biological sciences 20170921 10

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+ ...[more]

PMID: 29104491

Similar Datasets

Project description:The cardiac sodium (Na+)/calcium (Ca2+) exchanger (NCX1) is an electrogenic membrane transporter that regulates Ca2+ homeostasis in cardiomyocytes, serving mainly to extrude Ca2+ during diastole. The direction of Ca2+ transport reverses at membrane potentials near that of the action potential plateau, generating an influx of Ca2+ into the cell. Therefore, there has been great interest in the possible roles of NCX1 in cardiac Ca2+-induced Ca2+ release (CICR). Interest has been reinvigorated by a recent super-resolution optical imaging study suggesting that ~18% of NCX1 co-localize with ryanodine receptor (RyR2) clusters, and ~30% of additional NCX1 are localized to within ~120nm of the nearest RyR2. NCX1 may therefore occupy a privileged position in which to modulate CICR. To examine this question, we have developed a mechanistic biophysically-detailed model of NCX1 that describes both NCX1 transport kinetics and Ca2+-dependent allosteric regulation. This NCX1 model was incorporated into a previously developed super-resolution model of the Ca2+ spark as well as a computational model of the cardiac ventricular myocyte that includes a detailed description of CICR with stochastic gating of L-type Ca2+ channels and RyR2s, and that accounts for local Ca2+ gradients near the dyad via inclusion of a peri-dyadic (PD) compartment. Both models predict that increasing the fraction of NCX1 in the dyad and PD decreases spark frequency, fidelity, and diastolic Ca2+ levels. Spark amplitude and duration are less sensitive to NCX1 spatial redistribution. On the other hand, NCX1 plays an important role in promoting Ca2+ entry into the dyad, and hence contributing to the trigger for RyR2 release at depolarized membrane potentials and in the presence of elevated local Na+ concentration. Whole-cell simulation of NCX1 tail currents are consistent with the finding that a relatively high fraction of NCX1 (~45%) resides in the dyadic and PD spaces, with a dyad-to-PD ratio of roughly 1:2. Allosteric Ca2+ activation of NCX1 helps to "functionally localize" exchanger activity to the dyad and PD by reducing exchanger activity in the cytosol thereby protecting the cell from excessive loss of Ca2+ during diastole.

Dataset Information

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

Publications

Distinct Effects of Ca<sup>2+</sup> Sparks on Cerebral Artery and Airway Smooth Muscle Cell Tone in Mice and Humans.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets