alpha(1)- and beta-adrenoceptor-mediated increase in Rb-86(+)-uptake in isolated cardiomyocytes from adult rat heart: Evidence for interaction between the two receptor systems

The aim of the present investigation was to study the effect of alpha(1)- and beta-adrenoceptor stimulation, alone and in combination, on potassium uptake in isolated ventricular cardiomyocytes from adult rat heart, using the potassium analogue Rb-86(+). The reliability of Rb-86(+) as a potassium analogue was also investigated. alpha(1)-, beta-, And combined adrenoceptor stimulation was achieved by using noradrenaline in the presence and absence of appropriate adrenoceptor antagonists. The uptake of Rb-86(+) was found to increase linearly with time up to 20 min., both during basal and receptor-stimulated conditions. The basal uptake rate was about 0.18 ml/g protein X min. At 15 min. both alpha(1)-, beta- and combined adrenoceptor stimulation dose-dependently increased the Rb-86(+)-uptake with a -logEC(50) of 7.05, 6.68 and 6.73, respectively. The maximal increase in these series achieved by 5X10(-5) mol/l noradrenaline was 29%, 24% and 41% above basal lever, respectively. Comparison of the maximal effects in the same cell preparations, with the observed value for combined adrenoceptor stimulation in each experiment as 100%, gave a relative maximal increase in Rb-86(+)-uptake after separate alpha(1)-adrenoceptor stimulation of 67+/-8%, and of 68+/-6% after separate beta-adrenoceptor stimulation. The theoretically calculated value for combined adrenoceptor stimulation, if additivity, was 135+/-11%, which was significantly higher than the observed value (100%) (P=0.026). The effect of noradrenaline was not limited by the maximal Rb-86(+)-uptake capacity, as 10(-5) mol/l forskolin increased the Rb-86(+)-uptake more than noradrenaline. Examining the reliability of Rb-86(+) as potassium-analogue by combining K-42(+) and Rb-86(+) in the same experiments, showed that combined adrenoceptor stimulation dose-dependently increased both the (42)Ki(+)- and Rb-86(+)-uptake with the same potency and to the same extent. Thus Rb-86(+) is a reliable potassium-analogue for these effects. In conclusion both alpha(1)- and beta-adrenoceptor stimulation dose-dependently increased the cellular Rb-86(+)-uptake to the same extent and with the same potency. The observed maximal Rb-86(+)-uptake after combined adrenoceptor stimulation was significantly higher than the maximal effect after either form of separate receptor stimulation, but significantly lower than expected if the effects were purely additive. The results thus show inhibitory interaction between the two receptor systems.