Elucidation of Mechanisms in Cu (II) Caused Hypercontraction of Rat Tracheal Rings

• Published in: Biological trace element research Vol. 200; no. 3; pp. 1212 - 1219
• Main Authors: Afrin, Farah, Basir, Seemi Farhat, Khan, Luqman A.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.03.2022; Springer Nature B.V
• Subjects: Acetylcholine; Animals; Asthma; Biochemistry; Biomedical and Life Sciences; Biotechnology; Calcium; Calcium (intracellular); Calcium - pharmacology; Calcium Channel Blockers - pharmacology; Calcium channels; Calcium channels (voltage-gated); Calcium ions; Channels; Copper; Depletion; Explants; Intracellular; Ion channels; Life Sciences; Muscle Contraction; Muscle, Smooth; Muscles; Muscular function; Neurotransmitters; Nitric oxide; Nutrition; Oncology; Overdose; Prostaglandin endoperoxide synthase; Rats; Reactive oxygen species; Receptors; Respiratory diseases; Respiratory disorders; Smooth muscle; Toxicity; Transient receptor potential proteins; Tracheal rings; Voltage-operated Ca; channel; Nitric oxide synthase; Transient receptor potential channel; Copper chloride; Voltage-operated Ca2+ channel
• ISSN: 0163-4984; 1559-0720
• DOI: 10.1007/s12011-021-02718-x

Airway smooth muscle contraction is one of the primary factors involved in the initiation and progression of asthma which in turn is regulated by increased cytosolic Ca 2+ concentration from intracellular stores and through transmembrane ion channels. Calcium-independent factors such as reactive oxygen species (ROS) generation, nitric oxide (NO) depletion and cyclooxygenase (COX) pathways also contribute to tracheal smooth muscle contraction. Studies on copper toxicity suggest significance of this essential micronutrient overdose in acute respiratory disorders, allergic asthma and ciliary motion in tracheal explants. However, the mechanism of copper caused hypercontraction upon direct exposure to tracheal smooth muscle is largely unknown. In this study we investigate the effect of copper exposure on isolated tracheal rings and relative contributions of various factors in acetylcholine-induced contractions. Results obtained suggest that rise in intracellular calcium concentration via voltage-operated Ca 2+ channel (VOCC), store-operated Ca 2+ channel (SOCC), stretch-activated channels (SAC) and TRP channel (transient receptor potential channel) activation is the major factor in copper-mediated hypercontraction. ROS generation or COX-dependent pathways do not appear to significantly contribute to Cu 2+ caused hypercontraction.