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

It is reported here that DA causes prolonged inhibition associated with hyperpolarization and increased conductance, which would make DA effective in modulating the high frequency firing and burst generation which occurs normally in some neurones and pathologically in HPCs during epileptogenesis.

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 discharge2,3 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 projection4–6 and that DA inhibits most hippocampal neurones7,8. 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 neurones9,10, and pathologically in HPCs during epileptogenesis11.