Changes in cytosolic Ca2+ and contraction induced by various stimulants and relaxants in canine tracheal smooth muscle

Abstract

Effects of stimulants and relaxants on the cytosolic Ca2+ level [(Ca2+]cyt) and contraction were examined in isolated canine tracheal smooth muscle. High K+ and carbachol induced a sustained increase in [Ca2+]cyt and muscle tension. Cumulative addition of KCl induced a graded increase in [Ca2+]cyt and muscle tension. Cumulative addition of carbachol induced greater contraction than high K+ at a given [Ca2+]cyt 12-Deoxyphorbol 13-isobutyrate (DPB) (50 nmol/l) induced a small sustained contraction with little effect on [Ca2+]cyt. A higher concentration (1 mumol/l) of DPB induced a larger sustained contraction with a decrease in [Ca2+]cyt. DPB (50 nmol/l) potentiated the KCl-induced contraction without or with only a small additional increase in [Ca2+]cyt. By contrast, 1 mumol/l DPB potentiated the high-K(+)-induced contraction with a decrease in [Ca2+]cyt. Addition of 50 nmol/l or 1 mumol/l DPB in the presence of carbachol inhibited both [Ca2+]cyt and muscle tension. Verapamil, isoprenaline and forskolin did not change or slightly decreased [Ca2+]cyt and muscle tension in resting trachea. Verapamil inhibited the contraction and [Ca2+]cyt stimulated by high K+ and carbachol. Isoprenaline and forskolin inhibited the high-K(+)-induced contraction without changing [Ca2+]cyt, whereas these inhibitors inhibited carbachol-induced contraction with a relatively small decrease in [Ca2+]cyt. These results suggest that (a) sustained contractions induced by high K+ and carbachol are due to the sustained increase in [Ca2+]cyt, (b) carbachol increases the sensitivity of contractile elements to Ca2+, and (c) isoprenaline and forskolin inhibit the contraction by the decrease in [Ca2+]cyt and also by the decrease in the sensitivity of contractile elements to Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)