Protein kinase C activators block specific calcium and potassium current components in isolated hippocampal neurons

• Published in: The Journal of neuroscience Vol. 8; no. 11; pp. 4069 - 4078
• Main Authors: Doerner, D, Pitler, TA, Alger, BE
• Format: Journal Article
• Language: English
• Published: Washington, DC Soc Neuroscience 01-11-1988; Society for Neuroscience
• Subjects: Animals; Biochemistry and metabolism; Biological and medical sciences; calcium; Calcium Channels - drug effects; Calcium Channels - physiology; Cell Separation; Central nervous system; Diglycerides - pharmacology; Dihydropyridines - pharmacology; Electrophysiology; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Glycerides - pharmacology; Guinea Pigs; hippocampus; Hippocampus - cytology; Hippocampus - metabolism; Neurons - metabolism; Phorbol Esters - pharmacology; potassium; Potassium Channels - drug effects; Potassium Channels - physiology; protein kinase C; Protein Kinase C - metabolism; Vertebrates: nervous system and sense organs; Brain; Protein kinase C; Calcium; Rodentia; Central nervous system; Electrophysiology; Ionic current; Voltage clamp method; Vertebrata; Mammalia; Guinea pig; Protein kinase; Antagonist; Potassium; Hippocampus; Rhinencephalon
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.08-11-04069.1988

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.