PROBING EXCITATION‐CONTRACTION COUPLING IN TRACHEALIS SMOOTH MUSCLE WITH THE MYCOTOXIN CYCLOPIAZONIC ACID

SUMMARY1. 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, AChinduced 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 M2‐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+ stores with CPA and promotion of M2‐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.

PROBING EXCITATION‐CONTRACTION COUPLING IN TRACHEALIS SMOOTH MUSCLE WITH THE MYCOTOXIN CYCLOPIAZONIC ACID Journal Articles