Protein kinase C activators block specific calcium and potassium current components in isolated hippocampal neurons.
Whole-cell voltage-clamp techniques were used to study the effects of the protein kinase C (PKC) activators phorbol esters and OAG on Ca and K currents in differentiated neurons acutely dissociated from adult hippocampus and in tissue-cultured neurons from fetal hippocampus. PKC activators had selective depressant effects on K currents, with persistent currents (IK and IK-Ca) being reduced and transient current (IA) being unaffected. In both cell types we recorded both high-voltage-activated, noninactivating (L-type) and high-voltage-activated, rapidly inactivating (N-type) Ca current. A low-voltage-activated, rapidly inactivating (T-type) Ca current was also recorded in tissue-cultured neurons but not in acutely dissociated neurons. PKC activators markedly reduced N-type current with less effect on L-type and no effect on T-type Ca current. Effects of PKC activators could be reversed with washing or with application of PKC inhibitors H-7 or polymyxin-B, an effect that could not be attributed to inhibition of cAMP-dependent protein kinase. The Ca/calmodulin inhibitor calmidazolium was ineffective in reversing the actions of PKC activators. Using whole-cell voltage-clamp techniques, we have demonstrated that hippocampal neurons possess 3 distinguishable components of calcium current. Distinct K currents were also observed. Our data strongly support the hypothesis that both Ca and K currents are selectively regulated by PKC and that these effects occur directly on the postsynaptic neuron.
Doerner
D
D
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201.
Pitler
T A
TA
Alger
B E
BE
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D002469:Cell Separation; D004075:Diglycerides / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology; D004594:Electrophysiology; D004789:Enzyme Activation; D005989:Glycerides / Q000494:pharmacology*; D006168:Guinea Pigs; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*
D015220:Calcium Channels; D004075:Diglycerides; D004095:Dihydropyridines; D005989:Glycerides; D010703:Phorbol Esters; D015221:Potassium Channels; D011493:Protein Kinase C