Calcium-dependent atrial slow action potentials generated with phosphatidic acid or phospholipase D

Phosphatidic acid (PA) formed following phosphatidylinositol hydrolysis has been proposed as a necessary step in receptor-mediated Ca2+ flux. This study demonstrates that PA generates Ca2+-dependent slow action potentials (APs) in rat atrium partially depolarized with 22 mM K+. The slow response was not due to release of endogenous catecholamines or prostaglandin formation since propranolol and indomethacin failed to attenuate the PA-induced slow AP in normal and reserpinized rats. PA-induced slow APs demonstrated Ca2+-dependence such that increasing [Ca2+]o from 0.5 to 5.0 mM caused the amplitude of the slow AP to rise linearly with the logarithm of [Ca2+]o. Phospholipase D (PLD) but not phospholipase C, was able to induce a slow AP, possibly through PA formation. Adenosine attenuated the PA and PLD-induced slow response and aminophylline reversed these effects. The observation that PA and PLD generate Ca2+-dependent slow APs in depolarized rat atrium supports a role for PA mediating Ca2+ influx.