Cell membrane potential (Em) and isometric force development were measured simultaneously using isolated preparations of ferret tracheal smooth muscle in the study of the possible electromechanical effects on airway muscle of leukotriene-D4 (LTD4). At rest there was no spontaneous electrical or mechanical activity observed. LTD4 at 10(-10) molar (M) depolarized the cell membrane to minus 53+/-0.3 millivolts (mV) but caused no significant mechanical response. Depolarization to approximately minus 46+/-1mV was noted at a concentration of 10(-9)M and this elicited slow electrical oscillations as well. A concentration of 2x10(-5)M verapamil abolished these electrical oscillations. Verapamil also substantially decreased force generated by this concentration of LTD4 and abolished the phasic mechanical activity. Acetylcholine also depolarized and contracted ferret tracheal muscle in a concentration dependent manner. Diltiazem abolished these electrical oscillations and deceased the force generated by 5x10(- 6)M acetylcholine. Pretreatment of ferret tracheal muscle with 10(- 10)M LTD4 for 20 minutes potentiated both electrical and mechanical responsiveness of ferret airway muscle to subsequent acetylcholine stimulation. The authors conclude that there is an electrical basis for the slow, prolonged force generation of airway muscle caused by LTD4, and that LTD4 potentiates the electromechanical responsiveness of the airway muscle to muscarinic stimulation.
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