Bülbring, Edith

Abstract In the smooth muscle of guinea-pig uterus (oestrogen dominated) both noradrenaline (Nor) (α-action) and acetylcholine (ACh) depolarized the membrane, reduced membrane resistance, accelerated spike discharge and increased isometric tension proportionately. The magnitude of the response to ACh was directly related to the dose of ACh, the duration remaining that of the period of drug application. The response to Nor was slow in onset and outlasted the period of drug application by several minutes. Increasing doses of Nor mainly prolonged the duration of the response. The magnitude of the response depended on whether the depolarization by Nor reached firing threshold. The phasic tension response to evoked spikes was increased by Nor. Cooling reduced, and at 6°C abolished the depolarization caused by Nor but did not significantly change the response to ACh. The results obtained with variations of external potassium and chloride indicate that both ACh and Nor increased the membrane permeability to potassium, but that the Nor effect was small and shortlasting. Chloride was not involved in the depolarization caused by ACh, while the magnitude of depolarization and of the increase in membrane conductance by Nor were a direct function of the external chloride concentration. The removal of sodium from the external medium slowed the relaxation of the phasic tension responses to evoked spikes and increased resting tension. In the absence of spikes the tissue relaxed. The depolarization and reduction of membrane resistance by ACh were directly related to the external sodium concentration regardless whether sucrose or tris-Cl were used as substitute. The depolarization and reduction of membrane resistance by Nor did not depend on external sodium (tris substitution) though in the simultaneous absence of sodium and chloride (sucrose substitution) the response to Nor was abolished. The results obtained when NaCl was replaced with tris-Cl suggest that ACh may, in the absence of sodium, increase the entry of calcium. The failure of calcium removal from the cytoplasm may explain the maintained contracture. The contracture produced by Nor was increased in the absence of sodium, suggesting that, in addition to an increased calcium entry from outside, there may have been a release of sequestered calcium.

Abstract The α action of catecholamines on oestrogen dominated guinea-pig uterus is stimulant. The cell membrane is depolarized, membrane conductance is increased, spike discharge is accelerated and tension develops. This action resembles that of acetylcholine though catecholamines are less potent, and, in equiactive concentrations, catecholamines have a longer latency and a longer duration of action. Evidence, obtained by modifications of the ionic environment, indicates that the depolarization by acetylcholine is due to an increase in sodium and calcium permeability and that acetylcholine can release calcium from intracellular stores. The depolarization by catecholamines is due to an increase in chloride permeability and, in addition, sodium is required for the ensuing increase of spike discharge. Catecholamines produce an increase in the force of contraction, long outlasting their immediate stimulation. Moreover, their effect on membrane potential and membrane conductance persists in the presence of lanthanum. These results suggest that Ca release from intracellular stores may be the primary effect produced by the α action of catecholamines and that the increase in the cytoplasmic Ca2+ concentration may cause the changes at the cell membrane.