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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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