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 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.
Amoako
D
D
Department of Physiology, University of Hong Kong, Hong Kong.
Qian
Y
Y
Kwan
C Y
CY
Bourreau
J P
JP
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D007211:Indoles; D000252:Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid