The depressant effects of some amiloride analogues on the slow outward K + current and contraction of voltage-clamped frog muscle fibres

Abstract

The effects of 4 derivatives of amiloride, which are known to block the Na +/H + antiporter, were studied on the slow outward current (I so) and on tension development of voltage-clamped single muscle fibres of the frog Rana ridibunda. Each compound tested induced a strong depressant effect on tension and I so in a voltage-, time- and dose-dependent (10 −8 to 10 −5 M) manner at physiological pH. The effects exhibited a strong pH dependence (the greater the pH in the range between 6.6 and 8.0, the greater the depressant action). This seems to exclude the involvement of the Na +/H + antiport and alterations of surface membrane charges as mediators. The current block was not observed after the release of calcium from the sarcoplasmic reticulum was blocked with 75 μM tetracaine. It is concluded that the primary effect of the 4 compounds used was to inhibit the internal release of Ca 2+ from the sarcoplasmic reticulum, and that this inhibition blocked the Ca 2+-dependent slow outward current.