The spontaneous electrical and mechanical activity of human bronchial smooth muscle: Its modulation by drugs

Abstract

Tissue taken at operation was used to study the electrical and mechanical properties of human bronchial smooth muscle with intracellular microelectrodes and isometric recording of tension changes. Over 90% of the muscle strips exhibited spontaneous tone and 70% produced spontaneous phasic contractions. The resting membrane potential of the smooth muscle cells ranged between -40 to -50 mV with a mean value of -44.9 ± 5.2 mV (n = 92 ± s.d.). Spontaneous oscillations of the membrane potential (slow waves) were observed in 90% of the cells examined. The electrical slow waves, phasic contractions and spontaneous tone were greatly reduced by FPL 55712 (10-6 - 10-5 M). Indomethacin (1 - 5 x 10-5 M), atropine (10-6 M) or a 5-lipoxygenase inhibitor, AA 861 (5 x 10-6 M) each reduced spontaneous mechanical tone. Indomethacin and atropine each caused minor reduction in the amplitude of electrical slow waves. Leukotriene C4 (10-8 M), physostigmine (10-6 M) and K+-rich physiological salt-solution (containing atropine 10-6 M) each caused tone development in tissue treated with AA 861 (5 x 10-6 M). In the case of leukotriene C4 and physostigmine, phasic contractions were superimposed on the developed tone. Electrical field stimulation evoked an excitatory junction potential (e.j.p.) followed by a small group of slow waves. Repetitive field stimulation (2-20 stimuli at 20 Hz) markedly enhanced the amplitude of oscillatory slow waves. FPL 55712 (1.9 x 10-6 M) abolished the oscillatory slow waves following the e.j.p., and physostigmine (10-6 M) enhanced the amplitude of the e.j.p. and slow waves. These results indicate that, under in vitro conditions, the electrical activity of human bronchial smooth muscle comprises slow wave discharge which may be related to the spontaneous contractions and generation of basal tone.