Generation and Role of Oscillatory Contractions in Mouse Airway Smooth Muscle. 2018

Hao Xu, and Ping Zhao, and Wen-Jing Zhang, and Jun-Ying Qiu, and Li Tan, and Xiao-Cao Liu, and Qian Wang, and Xi Luo, and Yu-Shan She, and Dun-An Zang, and Bei-Bei Liu, and Lei Cao, and Xiao-Xue Zhao, and Yuan-Yuan Chen, and Meng-Yue Li, and Jinhua Shen, and Yong-Bo Peng, and Lu Xue, and Meng-Fei Yu, and Weiwei Chen, and Li-Qun Ma, and Gangjian Qin, and Qing-Hua Liu
Institute for Medical Biology, College of Life Sciences, South-Central University for Nationalities, Wuhan, China.

OBJECTIVE Tetraethylammonium chloride (TEA) induces oscillatory contractions in mouse airway smooth muscle (ASM); however, the generation and maintenance of oscillatory contractions and their role in ASM are unclear. METHODS In this study, oscillations of ASM contraction and intracellular Ca2+ were measured using force measuring and Ca2+ imaging technique, respectively. TEA, nifedipine, niflumic acid, acetylcholine chloride, lithium chloride, KB-R7943, ouabain, 2-Aminoethoxydiphenyl borate, thapsigargin, tetrodotoxin, and ryanodine were used to assess the mechanism of oscillatory contractions. RESULTS TEA induced depolarization, resulting in activation of L-type voltage-dependent Ca2+ channels (LVDCCs) and voltage-dependent Na+ (VNa) channels. The former mediated Ca2+ influx to trigger a contraction and the latter mediated Na+ entry to enhance the contraction via activating LVDCCs. Meanwhile, increased Ca2+-activated Cl- channels, inducing depolarization that resulted in contraction through LVDCCs. In addition, the contraction was enhanced by intracellular Ca2+ release from Ca2+ stores mediated by inositol (1,4,5)-trisphosphate receptors (IP3Rs). These pathways together produce the contractile phase of the oscillatory contractions. Furthermore, the increased Ca2+ activated the Na+-Ca2+ exchanger (NCX), which transferred Ca2+ out of and Na+ into the cells. The former induced relaxation and the latter activated Na+/K+-ATPase that induced hypopolarization to inactivate LVDCCs causing further relaxation. This can also explain the relaxant phase of the oscillatory contractions. Moreover, the depolarization induced by VNa channels and NCX might be greater than the hypopolarization caused by Na+/K+-ATPase alone, inducing LVDCC activation and resulting in further contraction. CONCLUSIONS These data indicate that the TEA-induced oscillatory contractions were cooperatively produced by LVDCCs, VNa channels, Ca2+-activated Cl- channels, NCX, Na+/K+ ATPase, IP3Rs-mediated Ca2+ release, and extracellular Ca2+.

UI MeSH Term Description Entries
D008297 Male Males
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D009119 Muscle Contraction A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001683 Biological Clocks The physiological mechanisms that govern the rhythmic occurrence of certain biochemical, physiological, and behavioral phenomena. Biological Oscillators,Oscillators, Endogenous,Pacemakers, Biological,Biologic Clock,Biologic Oscillator,Biological Pacemakers,Clock, Biologic,Clocks, Biological,Oscillator, Biologic,Oscillators, Biological,Pacemaker, Biologic,Pacemakers, Biologic,Biologic Clocks,Biologic Oscillators,Biologic Pacemaker,Biologic Pacemakers,Biological Clock,Biological Oscillator,Biological Pacemaker,Clock, Biological,Clocks, Biologic,Endogenous Oscillator,Endogenous Oscillators,Oscillator, Biological,Oscillator, Endogenous,Oscillators, Biologic,Pacemaker, Biological
D014132 Trachea The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. Tracheas
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D019789 Tetraethylammonium A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90) Tetraethylammonium Chloride,Tetraethylammonium Ion,Tetraethylammonium Bromide,Tetraethylammonium Hydroxide,Tetraethylammonium Iodide,Bromide, Tetraethylammonium,Chloride, Tetraethylammonium,Hydroxide, Tetraethylammonium,Iodide, Tetraethylammonium,Ion, Tetraethylammonium

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