The characteristics of tetraethylammonium-induced rhythmic contractions in canine tracheal smooth muscle: effect of Na-pump inhibition.

Abstract

Tetraethylammonium ions (TEA) induced rhythmic contractions (RC) in canine tracheal smooth muscle (frequency, 0.09 ± 0.01 contractions/min; tension development, 279 ± 36 mg/mg tissue wet weight, at a TEA concentration of 15 mM). The rhythmicity coupling with various electrical activities (e.g., oscillation or action potentials) was suppressed or reduced by metabolic depletion – anoxia, 2,4-dinitrophenol (DNP), monoiodoacetic acid (MIA), or KCN. DNP (3 × 10−6 M) or MIA (5 × 10−4 M) completely inhibited the RC. Anoxia or 1 mM KCN decreased the tension development by 50%. Under these conditions, basal tension was unaffected. During prolonged incubation in K+-free Krebs solution or in the medium containing 10−5 M ouabain in the presence of 10−7 M atropine, the tension development was minimal. Membrane potential was also unaffected by 1-h incubation with 10−5 M ouabain. In contrast, after the rhythmicity was induced by TEA, ouabain (1 × 10−6 to 3 × 10−6 M) was especially effective in depolarizing the membrane. At the same time, the RC was also changed into tonic contraction, which was relaxed by 10−6 M D 600 or 2.5 mM glycoletherdiamine-N,N,N′,N′-tetraacetic acid. An extracellular K+ concentration of 1–2 mM was necessary for initiation of the RC by TEA. Rb+ was as effective as K+, but Cs+ could not replace K+. When extracellular Na+ was substituted with Li+, the RC turned to tonic contraction. These results suggest that the Na pump takes part in the mechanism of the RC.It may be concluded that augmentation of membrane excitability and resulting excitation–contraction coupling in the presence of TEA can occur without the action of the Na pump, but that succession of the RC inevitably requires it.