An electrophysiological study of amiloride on sino-atrial node cells and ventricular muscle of rabbit and dog

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Abstract
Summary Effects of amiloride were studied on canine and rabbit sino-atrial node cells and the canine ventricular cells. 1. In the canine sino-atrial node selectively perfused with Tyrode solution through the sinus node artery, amiloride (4.4×10−4–1.3×10−2 mol/l) induced a negative chronotropic and a positive inotropic effect in a concentrationdependent manner. 2. In canine ventricular muscle, the amplitude of the action potential and the resting membrane potential were decreased in the presence of amiloride (4.4×10−6–8.7×10−4 mol/l). The maximum rate of rise was also depressed in a use-dependent manner as well as a concentration-dependent manner. Simultaneously the action potential duration was markedly prolonged. Low concentrations of amiloride decreased the contractile force, but higher concentrations (over 8.7×10−5 mol/l) enhanced it. 3. In the spontaneously beating rabbit sino-atrial node, amiloride (8.7×10−5–2.2×10−3 mol/l) lengthened the action potential duration and the cycle length accompanized with the decreases in the amplitude and the maximum rate of rise of the action potential. The maximum diastolic potential was slightly depolarized. 4. In voltage clamp experiments of the rabbit sino-atrial node, amiloride (4.4×10−4–1.3×10−3 mol/l) suppressed the slow inward current (I si) and the outward current (I k) concentration-dependently, without altering steady-state inactivation ofI si (f ∞) and the activation ofI k (p ∞). The hyperpolarization-activated inward current (I h) was also reduced. 5. These results suggest that amiloride decreasedI si,I k andI h by a reduction in the conductance of these current systems. The changes in the ionic currents must have contributed to produce the negative chronotropic and the positive inotropic actions of amiloride.