PKA and PKC enhance excitatory synaptic transmission in human dentate gyrus.
cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) are two major modulators of synaptic transmission in the CNS but little is known about how they affect synaptic transmission in the human CNS. In this study, we used forskolin, a PKA activator, and phorbol ester, a PKC activator, to examine the effects of these kinases on synaptic transmission in granule cells of the dentate gyrus in human hippocampal slices using whole-cell recording methods. We found that both forskolin and phorbol ester increased the frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs) but left the amplitude unaffected. Inactive forskolin and phorbol ester had no effect on sEPSCs in human dentate granule cells. Prior application of forskolin occluded the effects of phorbol ester on mEPSC frequency. Tetanic stimulation applied to the perforant path induced short-term depression in dentate gyrus granule cells. Both forskolin and phorbol ester significantly enhanced this short-term depression. Taken together, these results demonstrate that PKA and PKC are involved in up-regulation of excitatory synaptic transmission in human dentate granule cells, primarily by presynaptic mechanisms. In addition, the occlusion experiments suggest that the two kinases may share a common signal pathway.
Chen
Huan-Xin
HX
Department of Neurological Surgery and Evelyn F. and William L. McKnight Brain Institute, Gainesville, Florida 32610, USA.
Roper
Steven N
SN
D000293:Adolescent; D000328:Adult; D002648:Child; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D018891:Dentate Gyrus / Q000187:drug effects*; D004558:Electric Stimulation; D004594:Electrophysiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D020536:Enzyme Activators / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D018408:Patch-Clamp Techniques; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*
D020536:Enzyme Activators; D010703:Phorbol Esters; D017661:Receptors, Presynaptic; D005576:Colforsin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C