Mechanisms of Ionic Currents Involved in Suppressive Effect of Isoprenaline on the Action Potential of Guinea-Pig Vas Deferens in Normal Krebs Solution.

The effects of beta-adrenoceptor stimulation by isoprenaline (ISO) on action potential and membrane current were studied in the guinea-pig vas deferens in normal Krebs solution by using a double sucrose gap method. In current-clamp experiments, ISO produced the membrane hyperpolarization by reducing the resistance and modified the pattern of multi-spike activity elicited by long depolarizing currents; an initial spike potential was reduced in the amplitude and the rate of rising phases and the slope of diastolic depolarization was slowered, leading to a prolongation of the spike discharge interval. In voltage-clamp experiments, ISO greatly enhanced the late outward K+ current (Ik2) by increasing the conductance, but hardly affected the peak outward K+ current (Ik1). ISO also reduced the inward Ca2+ current (Ica) by decreasing the conductance (ga) as well as by reducing the driving force for Ca2+. While it increased the leakage conductance (g1) due to K+ associated with hyperpolarizing voltage steps. In the preparations treated with Ca2+ channel blocker such as D-600, the enhanced effect of ISO on the Ik was still prominent, suggesting that Ca2+ and K+ channels appear to be independently regulated during beta-adrenoceptor stimulation. These results suggest that ISO exerts depressant actions on the vas deferens muscle by reduction of the Ica as well as by prominent enhancement of the Ik2 via beta-adrenoceptor activation.