Induction of a myogenic response in tonic airway smooth muscle by tetraethylammonium

Abstract

In multi-unit tracheal smooth muscle (TSM), quick stretches applied at a velocity of 5 times the measured maximum velocity of isotonic shortening of the muscle, of a magnitude 3 times the measured extension of the series-elastic component when the muscle contracts maximally, and at optimal muscle length (L-o) were unable to elicit any myogenic response (MR). Experimental conditions such as hypoxia (P-O2 smaller than 60 mmHg) and acidosis (pH equals 6.8) or the presence of Ba2+ (2 mM), acetylcholine (10-6 M), or high (K+)-o (59 mM) were also unable to elicit the MR. However, tetraethylammonium chloride (TEA, 0.4-67 mM) produces 1) spontaneous phasic contractions and 2) a MR to quick stretch. The ionic basis for these changes was then investigated by studying the Ca and Mg dependence of the response to TEA. The dose-response relationship to TEA was shifted to the left by decreasing external Mg2+ from 2.5 to 0.5 mM. The ability of TSM to produce a MR was absolutely dependent on external Ca, but the threshold concentration required shifted from 2.5 times 10-5 M at normal external Mg (2.5 mM) to 5 times 10-4 M at the reduced external Mg (0.5 mM). The effects of TEA on spontaneity and the MR were abolished by D-600. These results suggest that 1) TEA functionally converts multiunit smooth muscle into a single unit one and leads to the development of a MR and 2) the MR results from a depolarization-activated mobilization of Ca and is inhibited by ionic conditions known to increase membrane permeability.