TY - JOUR
T1 - Neurotransmitter activation of inwardly rectifying potassium current in dissociated hippocampal CA3 neurons
T2 - Interactions among multiple receptors
AU - Sodickson, Deborah L.
AU - Bean, Bruce P.
PY - 1998/10/15
Y1 - 1998/10/15
N2 - 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 GABA(B) 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 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 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.
AB - 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 GABA(B) 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 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 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.
KW - Adenosine
KW - Baclofen
KW - GABA(B)
KW - GIRK
KW - Metabotropic glutamate receptor
KW - Serotonin
KW - Somatostatin
UR - http://www.scopus.com/inward/record.url?scp=0032531736&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032531736&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.18-20-08153.1998
DO - 10.1523/jneurosci.18-20-08153.1998
M3 - Article
C2 - 9763462
AN - SCOPUS:0032531736
VL - 18
SP - 8153
EP - 8162
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 20
ER -