The Journal of Neuroscience, January 15, 2000, 20(2):550-557
Arachidonic Acid Stimulates a Novel Cocaine-Sensitive Cation
Conductance Associated with the Human Dopamine Transporter
Susan L.
Ingram and
Susan G.
Amara
Vollum Institute and Howard Hughes Medical Institute, Oregon Health
Sciences University, Portland, Oregon 97201
The dopamine transporter (DAT) exhibits several ionic currents that
are either coupled to or uncoupled from the transport of substrate.
Second messenger systems have been shown to modulate dopamine (DA)
transport, however, the modulation of DAT-associated currents has not
been studied in depth. Using the two-electrode voltage-clamp method to
record from Xenopus oocytes expressing the human DAT, we
examined the effects of arachidonic acid (AA) on membrane currents. AA
(10-100 µM) stimulates a novel nonselective cation
conductance seen only in oocytes expressing human DA transporter (hDAT). The AA-stimulated conductance is up to 50-fold greater than the
current normally elicited by DA, but does not appear to arise from the
modulation of previously described hDAT conductances, including the
leak current and the current associated with electrogenic transport. In
addition, DA dramatically potentiates and cocaine blocks the
AA-stimulated DAT current. DA potentiates the AA-induced currents in
the absence of sodium and chloride, indicating that these currents
arise from processes distinct from those associated with substrate
transport. The effects of AA were mimicked by other fatty acids with a
rank order of potency correlated with their degree of unsaturation,
suggesting that AA directly stimulates the novel cation current.
Therefore, AA stimulation of this DAT-associated conductance may
provide a novel mechanism for modulation of neuronal signaling.
Key words:
dopamine; transporters; cocaine; nonselective cation
channels; arachidonic acid; fatty acids
Copyright © 2000 Society for Neuroscience 0270-6474/00/202550-08$05.00/0