Dopamine modulates the slow Ca(2+)-activated K+ current IAHP via cyclic AMP-dependent protein kinase in hippocampal neurons

Abstract

1. The effects of dopamine on the slow Ca(2+)-dependent K+ current (IAHP; AHP, afterhyperpolarization) and spike frequency adaptation were studied by whole cell voltage-clamp and sharp microelectrode current-clamp recordings in rat CA1 pyramidal neurons in rat hippocampal slices. 2. Dopamine suppressed IAHP in a dose-dependent manner, under whole cell voltage-clamp conditions. Similarly, under current-clamp conditions, dopamine inhibited spike frequency adaptation and suppressed the slow afterhyperpolarization. 3. The effect of dopamine on IAHP was mimicked by a D1 receptor agonist and blocked by dopamine receptor antagonists only in a minority of the cells. 4. Dopamine suppressed IAHP after blocking or desensitizing the beta-adrenergic receptors and, hence, did not act by cross-reacting with this receptor type. 5. The effects of dopamine on IAHP and spike frequency adaptation were suppressed by blocking the adenosine 3',5'-cyclic monophosphate (cAMP)-dependent kinase (PKA) with Rp-cAMPS and, hence, are probably mediated by the activation of this kinase. 6. We conclude that dopamine increases hippocampal neuron excitability, like other monoamine neurotransmitters, by suppressing IAHP and spike frequency adaptation, via cAMP and protein kinase A. The receptor type mediating this effect of dopamine remains to be defined.