Alpha-adrenoceptor-mediated effects of norepinephrine on the guinea pig sinus node

The significance of alpha-adrenergic-mediated effects of norepinephrine on cardiac pacemakers is still controversial. Sinus node preparations (SN) from guinea pig hearts were superfused with Tyrode's solution (36 degrees C) to investigate such actions. Intracellular microelectrodes were used to monitor sinus node rate and membrane potentials of SN subsidiary pacemaker fibers (SP). Membrane potentials were recorded before, during, and after 10 minutes of exposure to norepinephrine in low (10(-13)-10(-10) M) or high (10(-6) M) concentrations. Low norepinephrine did not modify the sinus node rate or the membrane potentials. High norepinephrine increased the sinus node rate as expected. In the presence of propranolol, high norepinephrine did not modify the sinus node rate, but the action potential duration of SP was increased, whereas the membrane resting potential and the amplitude of the action potential were unchanged. The alpha-adrenergic agonist methoxamine did not depress the automaticity of the sinus node preparations, but the antagonist phentolamine blocked the effect of high norepinephrine on the action potential duration. In summary, norepinephrine did not have an alpha-mediated action on the automaticity of the guinea pig sinus node preparations, but it did prolong the action potential duration through alpha-receptor stimulation. The conflicting results reported in the literature regarding the effects of alpha-adrenoceptor stimulation in the heart appear to be due to species differences in the number and/or affinity of receptors.