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Volume 16, Number 20,
Issue of October 15, 1996
pp. 6374-6385
Copyright ©1996 Society for Neuroscience
GABAB Receptor-Activated Inwardly Rectifying
Potassium Current in Dissociated Hippocampal CA3 Neurons
Received May 31, 1996; revised July 26, 1996; accepted July 30, 1996.
Deborah L. Sodickson and
Bruce P. Bean
Vollum Institute, Oregon Health Sciences University, Portland,
Oregon 97201, and Program in Neuroscience, Harvard Medical School,
Boston, Massachusetts 02115
GABA and the GABAB receptor agonist baclofen activated
a potassium conductance in acutely dissociated hippocampal CA3 neurons.
Baclofen-activated current required internal GTP, was purely potassium
selective, and showed strong inward rectification. As with
acetylcholine-activated current in atrial myocytes, external
Cs+ blocked inward but not outward current in a highly
voltage-dependent manner, whereas Ba2+ blocked with no
voltage dependence. Unlike the cardiac current, however, the
baclofen-activated current showed no intrinsic voltage-dependent
relaxation. With fast solution exchange, current was activated by
baclofen or GABA with a lag of ~50 msec followed by an exponential
phase (time constant ~225 msec at saturating agonist concentrations);
deactivation was preceded by a lag of ~150 msec and occurred with a
time constant of ~1 sec. GABA activated the potassium conductance
with a half maximally effective concentration (EC50) of 1.6 µM, much lower than that for activation of
GABAA receptor-activated chloride current in the same cells
(EC50 ~25 µM). At low GABA concentrations,
activation of the GABAB current had a Hill coefficient of
1.4-2.1, suggesting cooperativity in the receptor-to-channel pathway.
Although the maximal conductance activated by GABAB
receptors is much smaller than that activated by GABAA
receptors, its higher sensitivity to GABA and slower time course make
it well suited to respond to low concentrations of extra-synaptic
GABA.
Key words:
baclofen;
G-protein;
GIRK;
GABA;
GABAA;
chloride current;
cesium;
barium
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