Effects of amrinone on the transmembrane action potential of rabbit sinus node pacemaker cells

Effects of amrinone on the membrane action potential and spontaneous activity were investigated in sinus node pacemaker cells of rabbit heart by use of microelectrode techniques. Amrinone (1 X 10(-4) M to 6 X 10(-6) M) caused a shortening of cycle length of spontaneous firing (SPCL) accompanied by an increase in the maximum upstroke velocity at phase O (Vmax) and amplitude of action potential (AAP), while it did not affect the maximum diastolic potential (MDP). All the effects of amrinone on sinus node pacemaker cells were markedly attenuated or abolished in a low calcium medium (Ca+ 0.1 mM or 0.3 mM) or in the presence of the slow channel blocking agent, verapamil (5 X 10(-7) M, 2 X 10(-6) M). The effects of amrinone were not antagonized by the beta-adrenoceptor blocking agent, pindolol (2 X 10(-7) M). These results indicate that amrinone has an intrinsic effect on sinus node pacemaker cells, increasing their spontaneous firing activity. It is also assumed that the effects of amrinone on sinus node cells are probably mediated by an augmentation of the slow calcium and/or sodium inward current through the cell membrane.