Probing excitation-contraction coupling in trachealis smooth muscle with the mycotoxin cyclopiazonic acid

1. Muscarinic stimulation-induced tonic contraction of airway smooth muscle is independent of membrane potential, This contraction is not sensitive to inhibition by voltage-operated Ca2+ channel blockers or by K+ channel openers. 2. Cyclopiazonic acid (CPA) inhibits Ca2+ loading of internal stores but does not affect maximal tonic contraction induced by acetylcholine (ACh) in steady state conditions. 3. After depletion of internal Ca2+ stores with CPA, ACh-induced tonic contraction becomes dependent upon values of membrane potential, The contraction is then sensitive to voltage-operated Ca2+ channel blockers and to K+ channel openers. 4. Treatment of trachealis muscle with CPA potentiates the Mt-mediated component of ACh stimulation, but this potentiation is not entirely responsible for the switch in excitation-contraction (E-C) coupling. 5. It is proposed that depletion of internal Ca2+ teres with CPA and promotion of M(2)-stimulation can lead to a switch in E-C coupling in trachealis smooth muscle from pharmaco- to electromechanical mode, perhaps by targeting a plasma membrane K+ channel.