cyclic AMP-dependent protein Kinase enhances HIPPOCAMPAL DENTATE GRANULE
CELL GABA A receptor CURRENTS.
Kapur, Jaideep and Robert L. Macdonald.
Departments of Neurology* and Physiology, University of Michigan Medical
Center, Ann Arbor, Michigan 48104-1687, U.S.A..
APStracts 3:0123N, 1996.
SUMMARY AND CONCLUSIONS
1) The effects of activation of endogenous cAMP-dependent protein kinase
(PKA), intracellular application of PKA and inhibition of endogenous PKA by
protein kinase inhibitory peptide (PKIP) on hippocampal dentate granule cell
GABA A receptor (GABAR) currents were characterized. 2) GABAR currents evoked
by repeated application of GABA (30 or 100 [mu] M) were enhanced by
application of 1 mM norepinephrine (52 + 26%, n = 11) and of 500 [mu] M 8-
bromo cAMP (15 + 2%, n = 7). 3) GABA concentration response curves were
obtained from 6 dentate granule cells before and after application of 500 [mu]
M 8-bromo cAMP. The maximal current was increased significantly by 89 + 36 %,
but the mean EC 50 was not significantly changed (68 + 42 [mu] M vs. 25 + 10
[mu] M). 4) The GABA concentration response relationship was studied in a
group of 7 granule cells recorded with pipettes containing PKIP and 2 mM ATP
and compared with another group of 12 cells recorded with 2 mM ATP in the
pipette. When currents were recorded with intracellular PKIP, the mean EC 50
for GABA was no different (43 + 9 [mu] M vs. 45 + 16 [mu] M); however, the
maximal current obtained was smaller, (961 + 102 pA vs. 658 + 104 pA). 4)
Concentration response data were obtained from 4 granule cells using recording
pipettes containing the cPKA and an ATP regeneration system and compared with
7 cells recorded with the ATP regeneration system. With cPKA, the maximal
GABAR current was significantly larger (1224 + 132 pA vs. 718 + 56 pA), but
the EC 50 for GABA was not significantly altered (21 + 2.0 [mu] M vs. 79 + 25
Received 14 February 1996; accepted in final form 31 May 1996.
APS Manuscript Number J120-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 17 June 96