Control of the mode of excitation-contraction coupling by Ca2+ stores in bovine trachealis muscle

Abstract

Full muscarinic stimulation in bovine tracheal smooth muscle caused a sustained contraction and increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) that was largely resistant to inhibition by nifedipine. Depletion of internal Ca(2+) stores with cyclopiazonic acid resulted in an increased efficacy of nifedipine to inhibit this contraction and the associated increase in [Ca(2+)](i). Thus internal Ca(2+) store depletion promoted electromechanical coupling between full muscarinic stimulation and muscle contraction to the detriment of pharmacomechanical coupling. A similar change in coupling mode was induced by ryanodine even when it did not significantly modify the initial transient increase in [Ca(2+)](i) induced by this stimulation, indicating that depletion of internal stores was not necessary to induce the change in excitation-contraction coupling mode. Blockade of the Ca(2+)-activated K(+) channel by tetraethylammonium, charybdotoxin, and iberiotoxin all induced the change in excitation-contraction coupling mode. These results suggest that in this preparation, Ca(2+) released from the ryanodine-sensitive Ca(2+) store, by activating Ca(2+)-activated K(+) channels, plays a central role in determining the expression of the pharmacomechanical coupling mode between muscarinic excitation and the Ca(2+) influx necessary for the maintenance of tone.