Effect of cyclic adenosine monophosphate on the G protein-dependent inward rectifier K+-like channel current in medial prefrontal cortex pyramidal neurons

Cyclic adenosine monophosphate (camp) levels in medial prefrontal cortex (mpfc) pyramidal neurons are altered in neuropsychiatric disorders. camp is a component of the transduction pathways involved in the control of ionic channels by metabotropic receptors. the purpose of this study was to determine whether camp modifies the activity of the g protein-dependent inward rectifier k+ (girk)-like channel current in the mpfc pyramidal neurons of 3-week-old rats. channel currents were recorded in a patch clamp cell-attached configuration. membrane-permeable adenylyl cyclase activator forskolin (10 μm) and membrane-permeable protein kinase a (pka) activator 8-br-camp (100 μm) were found to significantly decrease the open probability (po) of the girk-like channels. conversely,selective protein kinase a inhibitors: h-89 (10 μm) and kt5720 (0.5 μm) increased the open probability of the girk-like channels. also,the effect of forskolin was tested after preincubation of the neurons with the pka inhibitor (kt5720). the application of forskolin,despite pka inhibition,significantly decreased the po of the girk-like channels. this finding suggested that girk-like channel current activity might also be inhibited by camp in a pka-independent manner. a compound,8cpt-2me-camp (10 μm),which is a specific activator of the epac protein,which in turn is another intracellular target of camp,was also found to inhibit girk-like channel activity. we conclude that the constitutive activity of neuronal girk-like channel currents is inhibited by camp. we suggest that pka and epac might be components of the transduction pathway between camp and the girk channels.