Dopamine modulates a Ca²⁺-activated potassium conductance in mammalian hippocampal pyramidal cells

Abstract

Dopamine (DA) is a neurotransmitter in the mammalian central nervous system which has proven or potential importance in such neurological disorders as parkinsonism, Huntington's chorea and epilepsy. Most of the electrophysiological data concerning the actions of DA in the brain have been obtained from studies in the caudate nucleus where DA produces neuronal depolarization and increased spike discharge¹, slow depolarization with decreased spike discharge^2,3 and an increase in apparent input resistance³ and hyperpolarization with reduced firing rate³. The mechanisms underlying these effects have not been examined. The evidence suggests that the hippocampus receives a dopaminergic projection^4–6 and that DA inhibits most hippocampal neurones^7,8. We have studied the effects of DA on CA1 hippocampal pyramidal cells (HPCs) in vitro and report here that DA causes prolonged inhibition associated with hyperpolarization and increased conductance. These effects seem to derive from induction of a Ca²⁺-activated K⁺ conductance, and would make DA effective in modulating the high frequency firing and burst generation which occurs normally in some neurones^9,10, and pathologically in HPCs during epileptogenesis¹¹.