Na+/K+ ATPase mediates rhythmic spontaneous relaxations in canine airway smooth muscle

In canine airway smooth muscle, cyclopiazonic acid (CPA; selective blocker of the sarcoplasmic reticulum Ca(2+)-pump) evokes a contractile response which is initially mediated via release of internally sequestered Ca2+, but is later supported almost exclusively by electromechanical coupling. As such, this second component is highly sensitive to inhibition of voltage-dependent Ca(2+)-influx (e.g. dihydropyridines, removal of external Ca2+) or to membrane hyperpolarization. In the present study, we describe relaxations which occur spontaneously during this second component of the CPA-evoked contraction. These relaxations are also electromechanically mediated, since they are abolished by depolarization of the membrane by high-K+ media. TEA has relatively little effect on the phasic activity, thus ruling out an involvement of Ca(2+)-dependent K+ channels. On the other hand, the phasic activity is abolished by ouabain, by removal of external K+, or by cooling and is markedly slowed by removal of external Na+. These observations indicate that the phasic activity is mediated by the Na+/K(+)-ATPase.