The action of isoprenaline on the smooth muscle of the guinea-pig taenia coli.

1. The beta-action of catecholamines on the smooth muscle of guinea-pig taenia coli was investigated by observing the effects of isoprenaline (2 X 10(-8)-7.2 X 10(-6) M) in the presence of an alpha-blocker, phentolamine (6.3 X 10(-6) M). Electrical and mechanical activity were recorded with the double sucrose gap method. Calcium and potassium fluxes were determined using the 45Ca and 42K isotopes. 2. Isoprenaline suppressed spontaneous spike generation, reduced the size of evoked phasic contractions, and caused a small hyperpolarization of the membrane without change in membrane resistance. These effects were abolished by a beta-blocker, propranolol (6.8 X 10(-6) M). 3. The hyperpolarization induced by isoprenaline was smaller in quiescent, nonstimulated muscle than in active, frequently stimulated preparations. It occurred with the same time course as the reduction in the size of evoked phasic contractions. Both effects were dose dependent and reached a maximum at 7.2 X 10(-7) M-isoprenaline. 4. Hyperpolarization by direct current application did not reduce the size of evoked phasic contractions until excitation threshold was reached. In the presence of isoprenaline, repolarization of the membrane to its original level by depolarizing current application did not restore the reduced phasic contractions to their original size. 5. The slopes of the current-voltage relation in the absence and presence of isoprenaline were parallel, confirming the absence of a change in membrane resistance. Isoprenaline also did not affect membrane resistance when applied in the modified ionic environments used. 6. In different external K concentrations (0.60-29.5 mM) the relationship between the size of the electrotonic potential and the magnitude of the isoprenaline-induced hyperpolarization was linear. A similar, direct relation was seen between isoprenaline hyperpolarization and membrane resistance when the latter was increased by lowering external chloride to 13.3 mM. 7. Excess Cao (7.5 mM) hyperpolarized the membrane and reduced membrane resistance, but the hyperpolarization by isoprenaline was larger than in normal solution, being inversely related to the membrane resistance. The hyperpolarization was directly related to the external Ca concentration, suggesting that the magnitude of the response to the beta-action might depend on the cytoplasmic Ca concentration. 8. In low external Na (18 mM-Nao) the beta-action was scarcely affected. Complete replacement of Na with choline increased membrane resistance, muscle tone and phasic contractions; in this condition the effects of isoprenaline were abolished. 9. When the Na pump was blocked by exposure to zero K, to ouabain, or to both simultaneously, isoprenaline remained highly effective. However, prolonged exposure to ouabain abolished the beta-action. 10. Isoprenaline (1.4 X 10(-6) M) increased 45Ca efflux by about 20%, while 45Ca influx was not changed, and 42K efflux remained constant. 11...