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

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The effects of β-adrenoceptor stimulation by isoprenaline (ISO) on action potential and membrane current were studied in the guinea-pig was 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 β-adrenoceptor stimulation. These results suggest that ISO exerts depressant actions on the was deferens muscle by reduction of the ICa as well as by prominent enhancement of the IK2 via β-adrenoceptor activation.