Please read Dr. Jude’s article in the American Journal of Respiratory Cell and Molecular Biology titled, “Starving a Cell Promotes Airway Smooth Muscle Relaxation: Inhibition of Glycolysis Attenuates Excitation-Contraction Coupling.“
The salient clinical feature of asthma, bronchospasm, is due primarily to agonist-induced airway smooth muscle (ASM) shortening. In ASM cells, the intracellular signaling cascades, collectively known as excitation–contraction (EC) coupling, evoke force generation. EC coupling can be semiquantitatively assessed in HASM cells by measuring the markers: increase in cytosolic Ca2+ and phosphorylation of MLC (myosin light chain) and MYPT1 (myosin phosphatase regulatory subunit 1). A variety of extrinsic and intrinsic factors modulate EC coupling in ASM cells to amplify airway hyperresponsiveness (AHR) in asthma. Our previous studies showed that cytokines, toxicants, and allergens amplify EC coupling in ASM cells to mediate AHR. Recently, we reported that human ASM (HASM) cells isolated from obese lung donors exhibited amplified contractile phenotype, characterized by elevated markers of EC coupling. However, the precise mechanisms driving amplified EC coupling in HASM cells remain poorly understood. To read the full article.
Starving a Cell Promotes Airway Smooth Muscle Relaxation: Inhibition of Glycolysis Attenuates Excitation-Contraction Coupling. Xu S, Karmacharya N, Woo J, Cao G, Guo C, Gow A, Panettieri RA Jr, Jude JA. Am J Respir Cell Mol Biol. 2023 Jan;68(1):39-48. PMID: 36227725 PMCID: PMC9817909 DOI: 10.1165/rcmb.2021-0495OC