ACTIONS OF VASOACTIVE-INTESTINAL-PEPTIDE AND NEUROPEPTIDE-Y ON THE PACEMAKER CURRENT IN CANINE PURKINJE-FIBERS

We have investigated the actions of vasoactive intestinal peptide (VIP ) and neuropeptide Y (NPY) on the pacemaker current (I-f) in canine Pu rkinje fibers. On voltage pulses to the middle of the I-f activation r ange, VIP reversibly increases I-f, whereas NPY reversibly decreases I -f. A three-pulse voltage protocol suggests that VIP shifts I-f activa tion in the positive direction and that NPY shifts I-f activation in t he negative direction on the voltage axis without changing maximal I-f conductance. These effects of VIP and NPY on I-f are exerted through their specific peptide receptors, since the effects are blocked by VIP and NPY receptor antagonists. VIP and NPY are colocalized in cardiac parasympathetic and sympathetic nerve endings, respectively, and can b e released preferentially on high and long-lasting nerve stimulation. Given this colocalization and frequency-dependent release, these resul ts suggest a role for these neuropeptides in controlling cardiac I-f a nd consequently heart rate.