Modulation of guinea pig intrinsic cardiac neurons by prostaglandins

Department of Biology, Ithaca College, Ithaca, New York 14850 Submitted 7 March 2003 ; accepted in final form 29 May 2003 Activation of cardiac mast cells has been shown to alter parasympathetic neuronal function via the activation of histamine receptors. The present study examined the ability of prostaglandins to alter the activity of guinea pig intracardiac neurons. Intracellular voltage recordings from whole mounts of the cardiac plexus showed that antigen-mediated mast cell degranulation produces an attenuation of the afterhyperpolarization (AHP), which was prevented by the phospholipase A 2 inhibitor 5,8,11,14-eicosatetraynoic acid. Exogenous application of either PGD 2 or PGE 2 produced a biphasic change in the membrane potential and an inhibition of both AHP amplitude and duration. Examination of prostanoid receptors using bath perfusions (1 µM PGE 2 and PGD 2 ), specific agonists (BW245C, sulprostone, and butaprost), and antagonists (AH6809 and SC19220) found evidence for both the PGE 2 -specific EP2 and EP3 receptors, but not for EP1 or the PGD 2 -specific prostanoid (DP) receptors. Sulprostone was able to mimic the PGE 2 responses in some cells, but not in all PGE 2 -sensitive cells. Butaprost was able to mimic the PG-induced hyperpolarization in some cells, but did not alter the AHP. Inhibition of specific potassium channels with either TEA, charybdotoxin, or apamin showed that neither TEA nor charybdotoxin could prevent the PGE 2 -induced AHP attenuation. Apamin alone inhibited AHP duration, with PGs having no further effect in these cells. These results demonstrate that guinea pig intracardiac neurons can be modulated by PG, most likely through either EP2, EP3, or potentially EP4 receptors, and this response is due, at least in part, to a reduction in small-conductance K Ca currents. parasympathetic; prostaglandin E 2 ; prostaglandin D 2 ; prostanoid receptor; K channels Address for reprint requests and other correspondence: J. C. Hardwick, Dept. of Biology, Ithaca College, Ithaca, NY 14850 (E-mail: jhardwick{at}ithaca.edu ).