Modulation of Ca2+ transients and contractile properties by beta-adrenoceptor stimulation in ferret ventricular muscles

Abstract

1. The mechanism of modulation of Ca2+ transients and contraction by beta-adrenoceptor stimulation was studied in ferret ventricular muscles using aequorin to measure intracellular Ca2+. 2. Peaks of tension and light transients were increased by isoprenaline (10(-9) - 5 x 10(-7) M) which also abbreviated their time courses. 3. Time-to-peak tension was significantly shortened by 5 x 10(-9) M-isoprenaline and time-to-peak light was abbreviated by 10(-9) M-isoprenaline. 4. The time for the light to decay was shortened at 10(-9) M-isoprenaline. However, a higher concentration of isoprenaline (10(-8) M) was required for significant shortening of the half-relaxation time (TR50). 5. When isoprenaline was removed and beta-blocker (bupranolol, 1 microM) was applied, the time course of the light transients recovered but the time course of relaxation did not recover. 6. The relationship between [Ca2+]i and tension in tetanic contraction produced in the presence of ryanodine (5 microM) was shifted to the right by isoprenaline (10(-8) M). This was recovered by the replacement of isoprenaline with bupranolol (1 microM). 7. Isoprenaline (10(-7) M) added to the solution containing 20 mM [Ca2+]O and Bay K 8644 (1 microM), which produced maximal tension, caused a large light signal and enhancement of the initial phasic tension in tetanic contraction. However, the replacement of isoprenaline with bupranolol after immersing the preparation in 20 mM [Ca2+]O solution with Bay K 8644 and isoprenaline, did not significantly change the tension level, although the light signal decreased. Similar results were obtained in the ventricular muscle of young rats. 8. These results suggest that the dose dependence of modulation of the contractile element and sarcoplasmic reticulum (SR) by beta-adrenoceptor stimulation differs, and that additional factors, other than the faster Ca2+ uptake by SR and the decrease in Ca2+ sensitivity of the contractile element, might be involved in the shortening of the half-relaxation time by beta-adrenoceptor stimulation. In addition, beta-adrenoceptor stimulation does not produce a marked change in the maximal tension level.