Electromechanical coupling of ferret airway smooth muscle in response to leukotriene C4

We investigated the possible electrophysiological basis for the slow, prolonged force generation by airway smooth muscle (ASM) produced by leukotriene C4 (LTC4). Preparations of ASM were made from ferret trachea and placed in tissue microchambers for study. Some of these preparations were arranged so that force transducers and intracellular microelectrodes (with tip resistances of 30-80 M omega) could be used to measure isometric force and cell membrane potential (Em) simultaneously from ASM cells stimulated by LTC4. We found that ferret tracheal muscle was relatively sensitive to LTC4 and that this sensitivity was not significantly affected by atropine (1 microM), phentolamine (1 microM), propranolol (3 microM), and pyrilamine (1 microM). In a 1 nM solution of LTC4, Em was -54.0 +/- 1.2 mV from 18 impalements (n) from 6 animals (N) compared with a base-line value of -61.6 +/- 0.8 mV (n/N = 29/8, P less than 0.0005). This change did not lead to force generation, however. Higher concentrations of LTC4 led to progressive decreases in Em to which force generation was closely coupled. Concentrations greater than or equal to 70 nM led to phasic oscillations in Em of 0.6-0.8 Hz and 1.7 mV in amplitude, which were abolished by 10 microM verapamil, although the base-line Em was unaffected by this concentration. Although 300 nM LTE4 by itself caused only a small depolarization of ferret trachealis, it substantially antagonized the electromechanical responsiveness of this smooth muscle to LTC4. We conclude that ferret ASM is relatively sensitive to LTC4 and that there is an electrical basis for the slow, prolonged force generation caused by this mediator.