Calcium and sodium dependence of the biphasic response of the guinea-pig ileum to agonists.

The isometric responses of the longitudinal smooth muscle of the guinea-pig ileum to acetylcholine and to histamine consist of a phasic contraction followed by a fade and a tonic contraction. At high agonist concentrations the fade is more pronounced and a period of lower tonus is observed in the early stage of the tonic component of the response. Experiments done in Ca2+-free medium indicate that the events responsible for the shape of the response take place in the absence of Ca2+ and of contraction. The phasic contraction was inhibited by hyperpolarization in low-Na+ medium. Small decreases in the external Na+ concentration caused a diminution of the fade. Reduction of the Na+ concentration during the early stages of the tonic response caused contraction whereas relaxation was observed at the late stages. It is proposed that the fade is dependent on a Na+-sensitive mechanism that is predominant at early but not at late stages of the responses to agonists.