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The Journal of Neurophysiology Vol. 83 No. 2 February 2000, pp. 1010-1018
Copyright ©2000 by the American Physiological Society
o
1Department of Neurobiology, Harvard Medical School; and 2Department of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts 02115
Greif, Gabriela J.,
Deborah L. Sodickson,
Bruce
P. Bean,
Eva J. Neer, and
Ulrike Mende.
Altered Regulation of Potassium and Calcium Channels by
GABAB and Adenosine Receptors in Hippocampal Neurons From
Mice Lacking G
o. J. Neurophysiol. 83: 1010-1018, 2000. To examine the role of
Go in modulation of ion channels by neurotransmitter
receptors, we characterized modulation of ionic currents in hippocampal
CA3 neurons from mice lacking both isoforms of G
o. In
CA3 neurons from G
o
/
mice,
2-chloro-adenosine and the GABAB-receptor agonist baclofen activated inwardly rectifying K+ currents and inhibited
voltage-dependent Ca2+ currents just as effectively as in
G
o+/+ littermates. However, the
kinetics of transmitter action were dramatically altered in
G
o
/
mice in that recovery on washout
of agonist was much slower. For example, recovery from
2-chloro-adenosine inhibition of calcium current was more than fourfold
slower in neurons from G
o
/
mice
[time constant of 12.0 ± 0.8 (SE) s] than in neurons from G
o+/+ mice (time constant of
2.6 ± 0.2 s). Recovery from baclofen effects was affected
similarly. In neurons from control mice, effects of both baclofen and
2-chloro-adenosine on Ca2+ currents and K+
currents were abolished by brief exposure to external
N-ethyl-maleimide (NEM). In neurons lacking
G
o, some inhibition of Ca2+ currents by
baclofen remained after NEM treatment, whereas baclofen activation of
K+ currents and both effects of 2-chloro-adenosine were
abolished. These results show that modulation of Ca2+ and
K+ currents by G protein-coupled receptors in hippocampal
neurons does not have an absolute requirement for G
o.
However, modulation is changed in the absence of G
o in
having much slower recovery kinetics. A likely possibility is that the
very abundant G
o is normally used but, when absent, can
readily be replaced by G proteins with different properties.
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