Abstract
Action mechanisms of the contractile agents, K, ACh and Ba and of the antispasmodics, Cd and Mn were investigated. The contractions by K, ACh and Ba are exponential in shape, but consisted of phasic contraction (PC) and the subsequent tonic contraction (TC). PC by K and ACh are initiated by the release and the passive influx of Ca, whereas the PC by Ba is due to the release of Ca. On the other hand, TC by these three agents is maintained by the active influx of Ca requiring energy. Since only the contraction by Ba remains constant in Ca (-) bath solution, it is assumed that the direct stimulation to muscle contractile elements without the mediation of Ca mobilization is also partly related to the contracting mechanism of Ba. Storage sites of Ca in the cell membrane of this preparation are distinguished into three divisions, the first, the second and the third, which contains loosely-, less loosely-, and tightly-bound Ca, respectively. K releases Ca to elicit contraction from the first division, ACh does so from the first and the second divisions, and Ba does so from all of the three divisions. The following assumption was obtained on the antispasmodic action of Cd and Mn, on the basis of the influence of Ca removal from bath solution and of addition of high K to bath solution and the analysis with concentration-action curves. The antispasmodic mechanism of Cd and Mn is due to inhibition of cell membrane (competitive inhibition of influx and then release of Ca and subsequently competitive and non-competitive inhibition of influx and release of Ca) followed by the non-competitive inhibition of muscle contractile system, with the increase of dosage.
