Relaxant actions of isoprenaline on guinea-pig isolated tracheal smooth muscle.

1. The effects of isoprenaline on membrane potential and intracellular Ca2+ concentration ([Ca2+]i) in guinea-pig isolated tracheal muscle were studied by use of intracellular micro-electrodes and fura-2 signals respectively. Measurements of membrane potential were carried out in the presence of spontaneously-generated muscle tone, whereas fura-2 signals were measured during contraction produced by exogenous prostaglandin E2 (100 nM). The potency of isoprenaline in causing relaxation was the same in these two different situations. 2. Isoprenaline (0.01 microM) produced relaxation accompanied by 5 mV hyperpolarization. A combination of tetraethylammonium (TEA, 10 mM) and verapamil (3 microM) did not alter the effects of isoprenaline. Removal of external K+ did not increase the degree of hyperpolarization produced by isoprenaline. 3. In the presence of TEA (10 mM) and verapamil (3 microM), isoprenaline (0.03-1 microM) reduced [Ca2+]i concentration-dependently. A similar degree of inhibition was observed when isoprenaline was applied during the maintained contraction induced by prostaglandin E2 and against the contraction evoked by the addition of Ca2+ to tissues bathed in a Ca(2+)-free medium and pretreated with both isoprenaline and prostaglandin E2. 4. It is concluded that activation of TEA-sensitive Ca(2+)-dependent K+ channels does not play a significant role in isoprenaline-induced relaxation. We propose that, in the guinea-pig tracheal muscle, isoprenaline may produce relaxation mainly by inhibiting a receptor-operated pathway for Ca2+ influx across the plasma membrane which is normally activated by prostaglandins.