Airway epithelial cells regulate membrane potential, neurotransmission and muscle tone of the dog airway smooth muscle

Abstract

1. The effects of epithelial cells were investigated on resting membrane potential and neuro-effector transmission in smooth muscle cells of the dog tracheal and bronchiolar tissues. 2. The mean value of the resting membrane potential of the epithelium-intact bronchiolar smooth muscle cells of the dog was--70.0 +/- 1.1 mV (+/- S.D., n = 40) and mechanical denudation of the epithelial layer depolarized the membrane to -57.0 +/- 2.5 mV (+/- S.D., n = 40). Application of isolated and dispersed epithelial cells (greater than 2 x 10(5) cells/ml) to the perfusing solution repolarized the membrane of epithelium-denuded bronchiolar smooth muscle cells to -67.0 +/- 2.7 mV (+/- S.D., n = 20). The mean resting membrane potential of the mucosa-free tracheal smooth muscle cells was -59.1 +/- 1.4 mV (+/- S.D., n = 50), and application of isolated and dispersed cells (greater than 2 x 10(5) cells/ml) hyperpolarized the membrane to -67.2 +/- 1.8 mV (+/- S.D., n = 50). These repolarizing actions were not modified by indomethacin (10(-5) M). 3. In the epithelium-denuded bronchioles, ACh (greater than 10(-9) M) dose-dependently depolarized the smooth muscle cells, while in the epithelium-intact bronchioles, ACh (10(-11) - 10(-8) M) did not affect the resting membrane potential. At a concentration of 10(-7) M, ACh significantly depolarized the membrane. 4. Electrical field stimulation (EFS; 50 microseconds in duration and about 10-20 V in strength) applied to ring preparations of the bronchioles evoked twitch-like contractions (hereafter referred as twitch contraction), and size of the twitch contractions gradually and continuously decreased in the presence or absence of indomethacin (10(-5) M) and guanethidine (10(-6) M). When similar experiments were performed using epithelium-denuded bronchiolar ring preparations, in no case was there a prominent reduction in the amplitude of the twitch contractions in the presence of indomethacin and guanethidine. 5. The decremental response of the twitch contraction observed in the epithelium-intact bronchioles was overcome by application of the leukotriene synthesis inhibitor AA861 (10(-6) M) and the leukotriene antagonist ONO1078 (10(-5) M). 6. Leukotrienes C4 and D4 (LTC4 and LTD4, greater than 10(-8) M) evoked muscle contraction with a steady increase in muscle tone, up to a certain level. However, at 10(-9) M, LTC4 increased and LTD4 decreased the amplitude of the twitch contractions evoked by EFS in the epithelium-intact bronchioles.(ABSTRACT TRUNCATED AT 400 WORDS)