ACTIVATION PROPERTIES OF CHEMICALLY SKINNED FIBERS FROM HUMAN ISOLATED BRONCHIAL SMOOTH-MUSCLE

1. The contractile activation properties of human isolated bronchial s mooth muscle were investigated using chemically (beta-escin) skinned s trips. 2. Concentration-dependent contractions were induced by free io n concentrations of Ca2+ (0.5-3 mu M), Sr2+ (2-200 mu M) and Ba2+ (50- 1000 mu M). The resulting -log[cation]-tension relationships were fitt ed by sigmoidal curves with EC(50) values (cation concentration requir ed to produce half-maximal tension) and co-operativity factors (Hill c oefficient, n(H)) of, respectively, 0.25 mu M and 3.4 for Ca2+, 12 mu M and 2.64 for Sr2+ and 100 mu M and 1.73 for Ba2+. Maximal responses to Sr2+ and Ba2+ were 125.5 +/- 15.4 and 96 +/- 8.1% (n=5) respectivel y of the maximum tension induced by Ca2+. 3. Trifluoperazine (5-100 mu M), cyclic BMP (50-300 mu M) and cyclic GMP (50-100 mu M) each antago nized Ca2+ in a concentration-dependent manner. On the other hand, oka daic acid (OA, 0.2-1 mu M) potentiated Ca2+ and increased the maximum response to Ca2+ (+25 +/- 5.4 %, n = 5, for 1 mu M OA). 4. This study has demonstrated the high Ca2+ sensitivity of the activation mechanism of human isolated bronchial smooth muscle. It also suggests that cont rol of the contractile machinery in the human bronchus involves proces ses of phosphorylation and dephosphorylation. The beta-escin-treated h uman bronchus may be a useful model for investigating the cellular bas is of some pathophysiological processes such as bronchial hyper-respon siveness.