Calcium and the alpha-action of catecholamines on guinea-pig taenia caeci.

Abstract

1. The involvement of calcium in the alpha-action of adrenaline on guinea-pig taenia caeci was studied by measuring the changes in membrane potential and muscle contraction, using the sucrose-gap method, and by determining the (42)K efflux, in the presence of a beta-blocker (propranolol, 1.8 x 10(-6)m).2. In the presence of extracellular calcium, the hyperpolarization caused by adrenaline (3 x 10(-6)m) was sustained during the period of its application (5 min), both in active preparations (at 36 degrees C) and in quiescent muscle (22 degrees C). In the absence of calcium, adrenaline caused a transient hyperpolarization which was smaller at 36 degrees C than at 22 degrees C and passed off within 5 min, while adrenaline was present.3. Both the sustained and the transient hyperpolarization were associated with an increase in (42)K efflux which had a similar time course. (42)K flux measurements were made in depolarized tissue (52.8 mm-potassium), in which the effect was consistent and more pronounced than in polarized muscle (2.8 mm-potassium).4. The transient hyperpolarization which is resistant to calcium removal and EGTA (0.1-2.0 mm) could be evoked only once but, following a short exposure to calcium (2.5 mm) for 20 sec and readmission of calcium-free medium, it was restored.5. The sustained and the transient hyperpolarization and the increase in (42)K efflux were abolished by the alpha-antagonist phentolamine (10(-5)m); their amplitude was dependent on the adrenaline concentration in the range 10(-7) to 3 x 10(-6)m, and both responses persisted in the absence of sodium or chloride.6. The hyperpolarization and the increase in (42)K efflux were greater at higher external calcium concentrations (0.3-2.5 mm).7. Cobalt (0.6 mm), D600 (2.5 x 10(-5)m) and the bee toxin apamin (10(-7)m) reduced the alpha-response.8. In the presence of apamin, in calcium-containing solution, the sustained hyperpolarization caused by adrenaline was preceded by, or converted to, depolarization, spike discharge and contraction.9. The depolarizing effect of adrenaline in the presence of apamin persisted in sodium-free or chloride-free medium, but was blocked in the absence of calcium and diminished by cobalt and D600.10. It is concluded that the alpha-response of guinea-pig taenia caeci consists of two components, both involving calcium. First, the activation of alpha-receptors increases calcium entry, which leads to the opening of potassium channels, a sustained hyperpolarization and inhibition of muscle activity. Secondly, in the absence of external calcium, a transient hyperpolarization is revealed, presumably due to the release of bound calcium from a limited cellular store which can be replenished by addition of external calcium, and this leads to an increase in potassium permeability.