Modulation of m2 receptors and excitation-contraction coupling in bovine airway smooth muscle

In airway smooth muscle, muscarinic stimulation is coupled to contraction independently of membrane potential. The consequence is that Ca++ channel blockers are ineffective in the treatment of airway diseases. Our earlier studies have shown that, following internal Ca++ stores depletion, coupling mechanism switches to membrane potential dependent and contraction is sensitive to voltage-dependent Ca++ channel blockers, in normal condition, M3 receptor stimulation is responsible for trachéal smooth muscle contraction while M2 receptors are silent. The aim of this study is to test whether switch in excitation-contraction coupling is due to modulation of M3 receptor to M3, following depletion of cyclopiazonic acid (CPA)- sensitive stores. In control medium, acetylcholine (ACh)-induced contraction was antagonized by 4DAMP (M3 antagonist) but not by gallamine (M2 antagonist). Following the depletion of the CPA sensitive stores, the potency of 4-DAMP decreased, while that of gallamine increased. Similarly, depletion of CPA sensitive stores and inhibition of M receptors, significantly increase the potency of cromakalim on AC h tonic contraction. Our results indicate that switch in excitation-contraction coupling observed following depletion of internal Ca++ stores only amplified M2 response and not modulation of M3 receptor.link_to_subscribed_fulltex