The effect of diazepam on atrial automaticity is not mediated by benzodiazepine receptors

The effect of diazepam on nomotopic cardiac automaticity was examined in the spontaneously beating isolated right atria of the rat. We also investigated whether "central"- or "peripheral"-type benzodiazepine receptors are involved and studied the role of calcium and adenosine in the possible effect of diazepam by the interaction of this drug with either GABA, picrotoxin, RO 15-1788, PK 11195, diltiazem or theophylline. Diazepam (400-500 microM) completely abolished atrial automaticity. This effect was not modified by the presence of either RO 15-1788 (30 microM), PK 11195 (0.1 microM), GABA (100 microM), picrotoxin (7 microM), theophylline (5 microM), diltiazem (0.6 microM) or hypercalcic media (3.6 mM). It is concluded that the diazepam-induced reduction of atrial frequency is mediated neither by "central"- nor "peripheral"- type benzodiazepine receptors, adenosine or calcium and could be due to a nonspecific interaction with the cell membrane.