Concentration-dependence of acetylcholine-induced changes in calcium and tension in swine trachealis

Abstract

Acetylcholine (ACh)-induced increases in intracellular calcium concentration ([Ca++]i) and tension were measured simultaneously in swine tracheal smooth muscle strips loaded with the calcium-sensitive fluorescent dye Fura-2. ACh at concentrations greater than or equal to 3 x 10(-8) M induced concentration-dependent increases in tension which reached a maximum at 10(-4) M. Increases in [Ca++]i occurred at all [ACh] tested (10(-8) to 10(-4) M). After addition of ACh at concentrations greater than 3 x 10(-7) M, [Ca++]i increased rapidly to a concentration dependent-peak then declined to a concentration-independent steady state approximately 250 nM above the resting [Ca++]i of 257 +/- 12 nM. There was a steep relationship (slope factor greater than 3) between the peak tension and the peak [Ca++]i reached at each [ACh]. The rate of decline of [Ca++]i to the steady state at [ACh] greater than 73 x 10(-7) M was well correlated with the peak [Ca++]i reached. We conclude that the peak increase in calcium induced by ACh sets the level of tension to be attained and the rate of decline of the transient increase in [Ca++]i. The steady-state [Ca++]i is sufficient for maintenance of tension.