Neurotransmitter Activation of Inwardly Rectifying Potassium Current in Dissociated Hippocampal CA3 Neurons: Interactions among Multiple Receptors
Journal of Neuroscience
We characterized potassium current activated by G-proteincoupled 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 Ba 2ϩ . The conductance had identical properties to that activated by GABA B receptors in the same cells. In onehalf of the CA3 neurons that were tested, the metabotropic glutamate agonist
... amate agonist 1S,3R-ACPD also activated inwardly rectifying Ba 2ϩ -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 GABA B -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 halfmaximally effective agonist concentrations were ϳ75 nM for somatostatin, ϳ100 nM for serotonin, and ϳ400 nM for 2-chloroadenosine. Dose-response relationships had Hill coefficients of 1.2-1.9, suggesting cooperativity in the receptor-tochannel 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.