Protein kinase inhibitors reduce GABA but not glutamate release in the nucleus accumbens.
We investigated the role of endogenous protein kinase activity on synaptic transmission in the rat nucleus accumbens slice. The isoquinolinesulfonamide H-7 (50muM), a non-selective serine/threonine protein kinase inhibitor, had no effect on pharmacologically isolated glutamatergic EPSCs. However, it reduced GABA release in a dose-dependent manner. This effect of H-7 was not mimicked by the selective cAMP-dependent protein kinase inhibitor H-89, the PKC inhibitor Bisindolylmaleimide-1, or the cGMP-dependent protein kinase inhibitor KT5823. However, bath application of the myosin light chain kinase (MLCK) inhibitor, ML-7, significantly reduced IPSC amplitudes and partially occluded the reduction in IPSCs observed following bath application of H-7. These results suggest that endogenous protein kinase activity, specifically MLCK activity, regulates GABA, but not glutamate release, onto medium spiny neurons in the nucleus accumbens.
Warrier
Ajithkumar
A
Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville, CA 94608, USA.
Hjelmstad
Gregory O
GO
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D047428:Protein Kinase Inhibitors; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine