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The Journal of Neuroscience, October 15, 1998, 18(20):8153-8162
Neurotransmitter Activation of Inwardly Rectifying Potassium
Current in Dissociated Hippocampal CA3 Neurons: Interactions among
Multiple Receptors
Deborah L.
Sodickson and
Bruce P.
Bean
Department of Neurobiology, Harvard Medical School, Boston,
Massachusetts 02115, and Vollum Institute, Oregon Health Sciences
University, Portland, Oregon 97201
We characterized potassium current activated by G-protein-coupled
receptors in acutely dissociated hippocampal CA3 neurons. Agonists for
serotonin, adenosine, and somatostatin receptors reliably activated a
potassium-selective conductance that was inwardly rectifying and that
was blocked by 1 mM external Ba2+. The
conductance had identical properties to that activated by GABAB receptors in the same cells. In one-half of the CA3
neurons that were tested, the metabotropic glutamate agonist
1S,3R-ACPD also activated inwardly
rectifying Ba2+-sensitive potassium current.
Activation of the current by serotonin and adenosine agonists occurred
with a time constant of 200-700 msec after a lag of 50-100 msec; on
removal of agonist the current deactivated with a time constant of 1-2
sec after a lag of 200-400 msec. These kinetics are similar to
GABAB-activated current and consistent with a direct action
of G-protein on the channels. For somatostatin, both activation and
deactivation were approximately fourfold slower, probably limited by
agonist binding and unbinding. The half-maximally effective agonist
concentrations were ~75 nM for somatostatin, ~100
nM for serotonin, and ~400 nM for
2-chloroadenosine. Dose-response relationships had Hill coefficients
of 1.2-1.9, suggesting cooperativity in the receptor-to-channel
coupling mechanism. At saturating concentrations of agonists, the
combined application of baclofen and either somatostatin, serotonin, or
2-chloroadenosine produced effects that were subadditive and often
completely occlusive. However, at subsaturating concentrations the
effects of baclofen and 2-chloroadenosine were supra-additive. Thus,
low levels of different transmitters can act synergistically in
activating inwardly rectifying potassium current.
Key words:
serotonin; somatostatin; adenosine; baclofen; metabotropic glutamate receptor; GABAB; GIRK
Copyright © 1998 Society for Neuroscience 0270-6474/98/18208153-10$05.00/0
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