MODIFICATION BY Ca⁺⁺ REMOVAL, Mg⁺⁺ AND Sr⁺⁺ OF THE MEMBRANE EFFECT AND THE INOTROPIC EFFECT OF NOREPINEPHRINE IN RABBIT LEFT ATRIA

¹ Department of Pharmacology, Faculty of Medicine, Kyoto University, Kyoto, Japan

The transmembrane potential and the isometric contraction were recorded from rabbit left atria driven electrically at 30 and 60/min. Removal of Ca⁺⁺ from bathing media decreased the resting potential and the overshoot, prolonged the 10% duration and diminished the force of contractions. The addition of Mg⁺⁺ (2.2 mM) shortened the action potential duration and did not restore contractions. Strontium ions (2.2 mM) when applied to Ca⁺⁺-free media increased the resting potential and the overshoot, prolonged the action potential duration and augmented the contractility. Norepinephrine (5 x 10^-7 to 10^-5 M) elicited an increase in the force of contractions but did not significantly influence parameters measured from atrial action potentials. However, at zero [Ca⁺⁺]_o norepinephrine markedly increased the magnitude and the duration of action potentials without modifying the resting potential. Under this condition norepinephrine restored contractions. Caffeine (up to 5 mM) did not restore the magnitude of action potentials and the contraction. The membrane effects and the inotropic effect of norepinephrine were inhibited by the addition of Mg⁺⁺ to Ca⁺⁺-free media. The inhibitory effect of Mg⁺⁺ was more apparent when the preparation was driven at 30/min than at 60/min. In solutions in which Ca⁺⁺ was substituted with Sr⁺⁺ action potential durations were prolonged by the amine. The contractile force at driving rates higher than 60/min was reduced by substitution of Sr⁺⁺ for Ca⁺⁺. Norepinephrine moved the force-rate curve upward in a dose-dependent manner.