Cooling-induced subsensitivity to carbachol in the tracheal smooth muscle of the guinea-pig

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Abstract
Summary Isolated tracheal strip-chain preparation of the guinea-pig was used to study the effect of temperature on carbachol-induced contraction. The preparation was suspended in the organ bath containing Krebs bicarbonate solution for isometric tension recording. A decrease of bath temperature from 37°C to 20°C (cooling) caused a transient increase in tension and thereafter inhibited the contractile response of the trachea caused by carbachol (30 nmol/l–3 μmol/l). Isosmotic potassium chloride (KCl, 64.7 mmol/l)-induced contraction or calcium chloride (CaCl2, 0.1–3 mmol/l)-induced contraction in K+-depolarized muscle was markedly inhibited by cooling. Verapamil in concentrations of 1 μmol/l or greater, which markedly depressed the CaCl2-induced contraction, caused partial depression of the contractile response to carbachol. On the other hand, carbachol-induced contraction of the trachea which was incubated with K+-rich, verapamil (3 μmol/l) containing Krebs solution and with Ca2+-free, EGTA (0.4 mmol/l) containing Krebs solution were both augmented at 20°C. From these observations, it is concluded that decreased responsiveness of the guinea-pig airway smooth muscle to carbachol with lowered temperature may be due to an inhibition of Ca2+ influx through voltage-dependent Ca2+ channels which involves part of the contraction.