Effects of L-glutamate on the responses to nerve stimulation in rat isolated atria

Abstract

In rat atria isolated with their sympathetic fibres the chronotropic responses to nerve stimulation with pulses of 2 ms duration were reduced in a concentration-dependent manner by 10 μM to 1 mM L-glutamte (glu) and by 0.01 to 1.00 μM (R,S)-3- hydroxy-5- methoxyloxasole-4- propionic acid (AMPA) , whereas they were unaffected by the other agonists of Glu receptors such as 1 μM to 1 mM N- methyl- D- aspartic acid (NMDA) , 10 μM to 1 mM kainate and 1 to 100 μM (±)-2-amino-4-phosphonobutyric acid (AP4). The reductions in the atrial responses to nerve stimulation caused by Glu were not accompanied by alterations in either the basal efflux of [ 3H]noradrenaline or its overflow in response to the stimulation. The sensitivity of the atria to exogenous noradrenaline was not modified by either Glu or AMPA. The decreases in the chronotropic responses caused by Glu and by AMPA were prevented by both the non-selective Glu receptor antagonist, 100 μM kynurenic acid, and the selective AMPA receptor antagonist, 10 to 50 μM 6,7-dinitroquinoxaline-2,3-dione (DNQX). In addition, the adenosine receptor antagonist, 8-phenyltheophylline (10 μM), as well as the muscarinic acetylcholine receptor antagonist, atropine (3 μM), prevented the inhibitory effects of both Glu and AMPA on the chronotropic responses of rat isolated atria. Since both adenosine and acetylcholine are known to exert negative inotropic and chronotropic effects in cardiac tissues, it is proposed that Glu could contribute, through the interaction with receptors of the AMPA type, to facilitate the release of adenosine and acetylcholine from the atria. The latter substances, in turn, could decrease the atrial rate. The location of the AMPA receptors in the rat heart as well as the sites where either acetylcholine or adenosine might act to exert their actions cannot be elicidated from the present results.