Evidence that Ca/calmodulin-dependent protein kinase mediates the modulation of the Ca2+-dependent K+ current,I AHP,by acetylcholine,but not by glutamate,in hippocampal neurons |
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Authors: | Pedarzani Paola Storm Johan F. |
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Affiliation: | (1) Institute of Neurophysiology, University of Oslo, PB 1104, N-0317 Blindern, Oslo, Norway;(2) Present address: Department of Molecular Biology of Neuronal Signals, Max-Planck-Institute for Experimental Medicine, Hermann-Rein-Strasse 3, D-37075 Göttingen, Germany |
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Abstract: | Muscarinic and metabotropic glutamate receptor agonists increase the excitability of hippocampal and other cortical neurons by suppressing the Ca2+-activated K+current,IAHP, which underlies the slow afterhyperpolarization (AHP) and spike frequency adaptation. We have examined the mechanism of action of a muscarinic agonist (carbachol) and a metabotropic glutamate receptor agonist (1-Aminocyclopentane-trans-1,3-dicarboxylic acid; t-ACPD) onIAHP in hippocampal CA1 neurons in slices, by using highly specific protein kinase inhibitors. We found that inhibition of protein kinase A (PKA) with the adenosine 3,5-cyclic monophosphate (cAMP) analogue Rp-adenosine-3,5-cyclic phosphorothioate Rp-cAMPS, did not prevent the muscarinic and glutamatergic suppression ofIAHP. In contrast, two specific peptide inhibitors of Ca2+/calmodulin-dependent protein kinase II (CaM-K II), each partially blocked the effect of carbachol, but not the effect of t-ACPD onIAHP. We conclude that CaM-K II, but not PKA, is involved in mediating the muscarinic suppression ofIAHP, although other pathways may also contribute. In contrast, neither CaM-K II nor PKA seems to mediate the metabotropic glutamate receptor action onIAHP. |
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Keywords: | Ca2+-activated K+current Afterhyperpolarization Hippocampus Muscarinic receptor Metabotropic glutamate receptor Protein kinase A Ca2+/calmodulin-dependent protein kinase II |
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