Dopamine decreases the calcium-activated afterhyperpolarization in hippocampal CA1 pyramidal cells

Abstract

The effect of dopamine (DA) on the calcium-activated potassium conductance underlying the slow afterhyperpolarization (AHP) which follows a train of action potentials in hippocampal pyramidal cells was studied utilizing the in vitro hippocampal slice preparation. Bath-applied DA (1-100 microM) significantly reduced the AHP in a reversible, dose-dependent manner. Neither the amount of current injected to elicit the AHP nor its initial amplitude had an effect on the reduction of the AHP by DA. DA did not depress calcium spikes, suggesting that the blockade of the AHP likely occurs at a step subsequent to the entry of calcium. Since DA's actions on the AHP closely mimicked those of norepinephrine, we examined the effect of beta-adrenergic antagonists on DA's actions. At concentrations which in other systems have been shown not to block DA stimulated adenylate cyclase, beta-adrenergic antagonists completely inhibited the reduction of the AHP by DA. In some cells DA also elicited small hyperpolarizations which were not blocked by application of dopamine receptor antagonists. These findings strongly suggest that a major electrophysiological action of DA in the hippocampus (i.e. blockade of the AHP) is due to its cross reactivity with beta-adrenergic receptors and that rigid pharmacologic criteria must be used before attributing an action of DA unambiguously to its interaction with DA receptors.