Protein kinase C regulates ionic conductance in hippocampal pyramidal neurons: electrophysiological effects of phorbol esters.
Proceedings of the National Academy of SciencesPublished 1 April 1985Open access
Jay M. Baraban, Solomon H. Snyder, Bradley E. Alger
Citations360
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
The potencies of several phorbol esters in exerting these actions paralleled their affinities for protein kinase C, suggesting that protein Kinase C regulates membrane ionic conductance.
Abstract
The vertebrate central nervous system contains very high concentrations of protein kinase C, a calcium- and phospholipid-stimulated phosphorylating enzyme. Phorbol esters, compounds with inflammatory and tumor-promoting properties, bind to and activate this enzyme. To clarify the role of protein kinase C in neuronal function, we have localized phorbol ester receptors in the rat hippocampus by autoradiography and examined the electrophysiological effects of phorbol esters on hippocampal pyramidal neurons in vitro. Phorbol esters blocked a calcium-dependent potassium conductance. In addition, phorbol esters blocked the late hyperpolarization elicited by synaptic stimulation even though other synaptic potentials were not affected. The potencies of several phorbol esters in exerting these actions paralleled their affinities for protein kinase C, suggesting that protein kinase C regulates membrane ionic conductance.
Keywords
MedicineNeuroscience
Journal of Biological ChemistryDirect activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters.
4,751 Citations1982Marco Castagna, Yoshimi Takai +4 more
Kinetic analysis indicates that TPA can substitute for diacylglycerol and greatly increases the affinity of the enzyme for Ca2+ as well as for phospholipid, and various phorbol derivatives which have been shown to be active in tumor promotion are also capable of activating this protein kinase in in vitro systems.
Biochemical JournalInositol trisphosphate and diacylglycerol as second messengers
3,528 Citations1984Michael J. Berridge
ScienceTurnover of Inositol Phospholipids and Signal Transduction
1,624 Citations1984Yasutomi Nishizuka
Various extracellular informational signals such as those from a group of hormones and some neurotransmitters appear to be passed from the cell surface into the cell interior by two routes, protein kinase C activation and Ca2+ mobilization.
Proceedings of the National Academy of SciencesPhorbol diester receptor copurifies with protein kinase C.
1,179 Citations1983J E Niedel, L J Kuhn +1 more
The phorbol diester receptor present in the particulate fraction of rat brain was solubilized by divalent ion chelation in the absence of detergents and partially purified by (NH4)2SO4 precipitation, DEAE-cellulose, and gel filtration chromatography.
Brain ResearchVoltage-clamp analysis of muscarinic excitation in hippocampal neurons
1,041 Citations1982J. V. Halliwell, Paul R. Adams
It is suggested that activation of cholinergic septal inputs to the hippocampus facilitates repetitive firing of pyramidal cells by turning off the M-conductance, without much change in the resting potential of the cell.
Journal of Biological ChemistryProtein kinase C as a possible receptor protein of tumor-promoting phorbol esters.
886 Citations1983Ushio Kikkawa, Yoshimi Takai +3 more
It is suggestive that protein kinase C is a phorbol ester-receptive protein, and the results presented seem to provide clues for clarifying the mechanism of tumor promotion.
Journal of Biological ChemistryStudies on a cyclic nucleotide-independent protein kinase and its proenzyme in mammalian tissues. II. Proenzyme and its activation by calcium-dependent protease from rat brain.
864 Citations1977Masatoshi Inoue, Akira Kishimoto +2 more
A protein kinase which phosphorylated histone and protamine was partially purified from bovine cerebellum and preliminary analysis suggested that the enzyme was produced from its precursor protein by a limited proteolytic reaction.
The Journal of PhysiologyControl of the repetitive discharge of rat CA 1 pyramidal neurones in vitro.
748 Citations1984Daniel V. Madison, R. A. Nicoll
It is concluded that accommodation of the action potential discharge of hippocampal pyramidal cells may be regulated by at least two potassium currents: the calcium‐activated potassium current and the M‐current.
Journal of Biological ChemistryC-kinase phosphorylates the epidermal growth factor receptor and reduces its epidermal growth factor-stimulated tyrosine protein kinase activity.
715 Citations1984Claude Cochet, Gordon N. Gill +3 more
Results indicate that, in A431 cells exposed to tumor promoters, C-kinase catalyzes phosphorylation of a significant population of EGF receptor molecules, which results in decreased self-phosphorylated EGF receptors both in vivo and in vitro and in decreased EGF-stimulated tyrosine kinase activity in vivo.
Journal of Biological ChemistryStudies on a cyclic nucleotide-independent protein kinase and its proenzyme in mammalian tissues. I. Purification and characterization of an active enzyme from bovine cerebellum.
596 Citations1977Yoshimi Takai, Akira Kishimoto +2 more
A protein kinase which phosphorylated histone and protamine was partially purified from bovine cerebellum and suggested that the enzyme was produced from its precursor protein by a limited proteolytic reaction.
NatureNoradrenaline blocks accommodation of pyramidal cell discharge in the hippocampus
588 Citations1982Daniel V. Madison, R. A. Nicoll
It is found that NA and cyclic AMP block the Ca2-activated K+ conductance in hippocampal pyramidal cells and that this blockade occurs at a step subsequent to the entry of Ca2+ into the neurone, which greatly increases the number of spikes elicited by a depolarizing stimulus.
Proceedings of the National Academy of SciencesCalcium-dependent protein kinase: widespread occurrence in various tissues and phyla of the animal kingdom and comparison of effects of phospholipid, calmodulin, and trifluoperazine.
572 Citations1980J.F. Kuo, Rolf G. G. Andersson +7 more
It is suggested that phospholipid-sensitive Ca2-dependent protein kinase may mediate certain actions of Ca2+ in tissues, acting independently or in a complementary manner with other protein phosphorylation systems stimulated by calmodulin-Ca2+, cyclic AMP, or cyclic GMP.
Journal of NeurophysiologyA calcium-activated hyperpolarization follows repetitive firing in hippocampal neurons
572 Citations1980John R. Hotson, David A. Prince
The Journal of PhysiologyFeed‐forward dendritic inhibition in rat hippocampal pyramidal cells studied <i>in vitro</i>
528 Citations1982Bradley E. Alger, Roger A. Nicoll
Intracellular recordings from CA1 pyramidal cells in the rat hippocampal slice preparation have been used to study the neuronal pathways involved in hippocampal synaptic inhibition.
NatureEnhancement of calcium current in Aplysia neurones by phorbol ester and protein kinase C
478 Citations1985Susan A. DeRiemer, J.A. Strong +3 more
Evidence is presented that activation of endogenous protein kinase C by the tumour-promoting phorbol ester TPA, or intracellular injection of the purified enzyme, enhances the voltage-sensitive calcium current in bag cell neurones of the mollusc Aplysia.
ScienceEpileptiform Burst Afterhyperpolarization: Calcium-Dependent Potassium Potential in Hippocampal CA1 Pyramidal Cells
436 Citations1980Bradley E. Alger, R. A. Nicoll
The afterhyperpolarization produced in the presence of y-aminobutyric acid antagonists is associated with a conductance increase and is inhibitory and has implications for understanding the cellular mechanisms of epilepsy.
NatureHistamine and noradrenaline decrease calcium-activated potassium conductance in hippocampal pyramidal cells
413 Citations1983Helmut L. Haas, Arthur Konnerth
A rapid and reversible decrease of the late AHP component is reported following a burst of sodium spikes or a calcium spike, during perfusion with micromotor concentrations of histamine and noradrenaline, and occurred in the absence of changes in the calcium spike.
ScienceAcetylcholine Mediates a Slow Synaptic Potential in Hippocampal Pyramidal Cells
375 Citations1983A. E. Cole, R. A. Nicoll
These findings provide electrophysiological support for the role of acetylcholine as a synaptic transmitter in the brain and demonstrate that nonclassical synaptic responses involving the blockade of membrane conductances exist in thebrain.
Proceedings of the National Academy of SciencesSpecific binding of phorbol ester tumor promoters
361 Citations1980Paul E. Driedger, Peter M. Blumberg
The data suggest that biological responses to thephorbol esters in chicken embryo fibroblasts are mediated by this binding activity and that the binding activity corresponds to the phorbol Ester target in mouse skin involved in tumor promotion.
The Journal of PhysiologyA bicuculline‐resistant inhibitory post‐synaptic potential in rat hippocampal pyramidal cells in vitro.
331 Citations1984Nigel R. Newberry, Roger A. Nicoll
It is concluded that the late hyperpolarizing potential is a bicuculline‐resistant i.p.s.p., which follows the gamma‐aminobutyric acid‐mediated inhibitory post‐synaptic potential and is involved in controlling the interval between bursts of epileptiform bursts.
Proceedings of the National Academy of SciencesPhorbol esters stimulate the phosphorylation of receptors for insulin and somatomedin C.
293 Citations1983Steven Jacobs, N Sahyoun +2 more
The results suggest a possible role of protein kinase C in regulating insulin and somatomedin C receptors and indicate that at least some of the residues phosphorylated by these two agents are distinct.
FEBS LettersThe phorbol ester TPA increases the affinity of exocytosis for calcium in ‘leaky’ adrenal medullary cells
271 Citations1983D. E. Knight, P. F. Baker
Exposure of ‘leaky’ bovine adrenal medullary cells to the phorbol ester TPA causes a shift in the calcium‐activation curve to lower calcium concentrations without altering the levels of secretion at the extremes of the activation curve, consistent with a role for protein kinase C in exocytosis.
Biochemical and Biophysical Research CommunicationsPhorbol diesters promote β-adrenergic receptor phosphorylation and adenylate cyclase desensitization in duck erythrocytes
237 Citations1984David R. Sibley, Ponnal Nambi +2 more
A potential role for protein kinase C in regulating beta-adrenergic receptor function is suggested in regulatingalpha-phorbol diesters or catecholamines and in promoting adenylate cyclase desensitization in duck erythrocytes with tumor promotion.
Proceedings of the National Academy of SciencesPhorbol ester induces desensitization of adenylate cyclase and phosphorylation of the beta-adrenergic receptor in turkey erythrocytes.
234 Citations1984D J Kelleher, Jeffrey E. Pessin +2 more
The findings indicate that decreased receptor-Ns coupling is correlated with receptor phosphorylation and that phorbol esters can influence the responsiveness of hormone-sensitive adenylate cyclase in certain cell types.
Proceedings of the National Academy of SciencesTumor promoters block tyrosine-specific phosphorylation of the epidermal growth factor receptor.
218 Citations1984B Friedman, A. Raymond Frackelton +5 more
A correlation between modulation of EGF receptor binding and phosphorylation of tyrosine by tumor promoters is demonstrated, suggesting a possible role for protein kinase C, the putative cellular receptor for these tumor promoters, in the mechanism of action.
Neuroscience LettersReceptor autoradiography with tritium-sensitive film: Potential for computerized densitometry
207 Citations1981José Palacios, Debra L. Niehoff +1 more
Benzodiazepine receptors mounted tissue sections of brain were localized by autoradiography using a tritium-sensitive sheet film (3H-Ultrofilm, LKB), which had many advantages compared to a previous technique utilizing emulsion-coated coverslips.
Biochemical PharmacologyMechanism of action of the phorbol ester tumor promoters: Specific receptors for lipophilic ligands
205 Citations1984Peter M. Blumberg, Susan Jaken +5 more
Heterogeneity of phorbol ester binding is demonstrated by reconstitution of apo-receptor into a heterogeneous lipid environment and an outstanding issue is whether protein kinase C is the phorbl ester receptor or whether it is only the most abundant class of receptor.
Journal of Neuroscience MethodsA simple chamber for recording from submerged brain slices
190 Citations1981Roger A. Nicoll, Bradley E. Alger
The construction of a chamber is described for stable intracellular recording from submerged brain slices while switching solutions, which is simple and inexpensive to make and is simple to use.
Journal of NeurophysiologyCharacteristics of a slow hyperpolarizing synaptic potential in rat hippocampal pyramidal cells in vitro
180 Citations1984Bradley E. Alger
An orthodromically evoked late hyperpolarizing potential (LHP) was studied using intracellular recording techniques in rat hippocampal CA1 pyramidal cells in vitro and was not found to be dependent on the excitatory postsynaptic potential (EPSP).
The Journal of Cell BiologyCa2+-dependent and -independent release of neurotransmitters from PC12 cells: a role for protein kinase C activation?
178 Citations1984Tullio Pozzan, G. Gatti +3 more
Activation of protein kinase C seems to play an important role in the regulation of exocytosis in neurosecretory cells, possibly by increasing and maintaining the sensitivity to Ca2+ of the intracellular apparatus regulating granule discharge by exocyTosis.
Proceedings of the National Academy of SciencesPhorbol ester effects on neurotransmission: interaction with neurotransmitters and calcium in smooth muscle.
150 Citations1985Jay M. Baraban, R J Gould +2 more
Brain ResearchEffects of tea on hippocampal neurons
135 Citations1980Philip A. Schwartzkroin, David A. Prince
Brain ResearchEvidence for two types of afterhyperpolarization in CA1 pyramidal cells in the hippocampus
110 Citations1981B. Gustafsson, H. Wigstro ̈m
Life SciencesCharacterization of neurotransmitter receptor-mediated phosphatidylinositol hydrolysis in the rat hippocampus
85 Citations1984Aaron Janowsky, Rodrigo Labarca +1 more
The results suggest that the measurement of agonist-induced [3H]-myo-inositol-1-phosphate accumulation, in the presence of lithium, represents a sensitive method for studying a number of receptor-mediated events in brain.
PubMedSpecific binding of [20-3H]12-deoxyphorbol 13-isobutyrate to phorbol ester receptor subclasses in mouse skin particulate preparations.
53 Citations1983Joseph A. Dunn, Peter M. Blumberg
Comparison of binding by [3H]DPB with that by the typical phorbol ester [20-3H].phorbol 12,13-dibutyrate indicated that PDBU also bound to the sites recognized by DPB, with affinities of 0.7 and 10 nM, respectively.
Cancer LettersRegional localization ny light microscopic autoradiography of receptors in mouse brain for phorbol ester tumor promoters
26 Citations1983Denise S. Nagle, Peter M. Blumberg
The distribution of receptors in mouse brain by light microscopic autoradiography suggests a functional role for the receptors within brain, and it permits comparison with other known activities.