Differential roles of Ca2+/calmodulin-dependent kinases in posttetanic potentiation at input selective glutamatergic pathways.

The electrosensory lateral line lobe (ELL) of the electric fish Apteronotus leptorhynchus is a layered medullary region receiving electroreceptor input that terminates on basal dendrites of interneurons and projection (pyramidal) cells. The molecular layer of the ELL contains two distinct glutamatergic feedback pathways that terminate on the proximal (ventral molecular layer, VML) and distal (dorsal molecular layer) apical dendrites of pyramidal cells. Western blot analysis with an antibody directed against mammalian Ca2+/calmodulin-dependent kinase 2, alpha subunit (CaMK2alpha) recognized a protein of identical size in the brain of A. leptorhynchus. Immunohistochemistry demonstrated that CaMK2 alpha expression in the ELL was restricted to fibers and terminals in the VML. Posttetanic potentiation (PTP) could be readily elicited in pyramidal cells by stimulation of either VML or DML in brain slices of the ELL. PTP in the VML was blocked by extracellular application of a CaMK2 antagonist (KN62) while intracellular application of KN62 or a CaMK2 inhibitory peptide had no effect, consistent with the presynaptic localization of CaMK2 alpha in VML. PTP in the dorsal molecular layer was not affected by extracellular application of KN62. Anti-Hebbian plasticity has also been demonstrated in the VML, but was not affected by KN62. These results demonstrate that, while PTP can occur independent of CaMK2, it is, in some synapses, dependent on this kinase.

[1]  Thomas J. Carew,et al.  Multiple overlapping processes underlying short-term synaptic enhancement , 1997, Trends in Neurosciences.

[2]  P. Kelly,et al.  Attenuation of paired-pulse facilitation associated with synaptic potentiation mediated by postsynaptic mechanisms. , 1997, Journal of neurophysiology.

[3]  P. Greengard,et al.  Immunocytochemical localization of calcium/calmodulin-dependent protein kinase II in rat brain. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[4]  C. Koch,et al.  From stimulus encoding to feature extraction in weakly electric fish , 1996, Nature.

[5]  L. Maler,et al.  Excitatory amino acid receptors at a feedback pathway in the electrosensory system: implications for the searchlight hypothesis. , 1997, Journal of neurophysiology.

[6]  WG Regehr,et al.  A quantitative analysis of presynaptic calcium dynamics that contribute to short-term enhancement , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[7]  T. Sihra,et al.  Ca/Calmodulin-dependent kinase II inhibitor KN62 attenuates glutamate release by inhibiting voltage-dependent Ca2+-channels , 1995, Neuropharmacology.

[8]  R Llinás,et al.  Intraterminal injection of synapsin I or calcium/calmodulin-dependent protein kinase II alters neurotransmitter release at the squid giant synapse. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[9]  H. Tokumitsu,et al.  KN-62, 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazi ne, a specific inhibitor of Ca2+/calmodulin-dependent protein kinase II. , 1990, The Journal of biological chemistry.

[10]  D W Tank,et al.  A quantitative measurement of the dependence of short-term synaptic enhancement on presynaptic residual calcium , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  R S Zucker,et al.  Calcium in motor nerve terminals associated with posttetanic potentiation , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[12]  L. Maler,et al.  In vitro plasticity of the direct feedback pathway in the electrosensory system of Apteronotus leptorhynchus. , 1997, Journal of neurophysiology.

[13]  R. Porter,et al.  Inhibition of voltage-gated Ca2+ channel activity in small cell lung carcinoma by the Ca2+/calmodulin-dependent protein kinase inhibitor KN-62 (1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperaz ine) . , 1995, Biochemical pharmacology.

[14]  P. Kelly,et al.  Regulation of synaptic facilitation by postsynaptic Ca2+/CaM pathways in hippocampal CA1 neurons. , 1996, Journal of neurophysiology.

[15]  Leonard Maler,et al.  The immunocytochemical localization of glutamate in the electrosensory system of the gymnotiform fish,Apteronotus leptorhynchus , 1994, Brain Research.

[16]  P. Greengard,et al.  A Novel Synaptic Vesicle‐Associated Phosphoprotein: SVAPP‐120 , 1991, Journal of neurochemistry.

[17]  T. Soderling,et al.  Characterization of Ca2+/calmodulin-dependent protein kinase IV. Role in transcriptional regulation. , 1994, The Journal of biological chemistry.

[18]  Alcino J. Silva,et al.  Deficient hippocampal long-term potentiation in alpha-calcium-calmodulin kinase II mutant mice. , 1992, Science.

[19]  Joseph Bastian,et al.  Descending control of electroreception. I. Properties of nucleus praeeminentialis neurons projecting indirectly to the electrosensory lateral line lobe , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[20]  S. Fleischer,et al.  Phosphorylation Modulates the Function of the Calcium Release Channel of Sarcoplasmic Reticulum from Cardiac Muscle (*) , 1995, The Journal of Biological Chemistry.

[21]  R. Zucker.  Short-term synaptic plasticity. , 1989 .

[22]  R. Greenspan,et al.  Concomitant alterations of physiological and developmental plasticity in drosophila CaM kinase II-inhibited synapses , 1994, Neuron.

[23]  H. Towbin,et al.  Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[24]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[25]  M. Popoli.  Synaptotagmin is endogenously phosphorylated by Ca2+/calmodulin protein kinase II in synaptic vesicles , 1993, FEBS letters.

[26]  K. A. Thomson,et al.  The Ca++/calmodulin-dependent protein kinase II inhibitors KN62 and KN93, and their inactive analogues KN04 and KN92, inhibit nicotinic activation of tyrosine hydroxylase in bovine chromaffin cells. , 1996, Biochemical and biophysical research communications.

[27]  D. McKay,et al.  Effects of Protein Kinase Inhibitors on Morphology and Function of Cultured Bovine Adrenal Chromaffin Cells: KN‐62 Inhibits Secretory Function by Blocking Stimulated Ca2+ Entry , 1996, Journal of neurochemistry.

[28]  P. Stanton,et al.  Distinct synaptic loci of Ca2+/calmodulin-dependent protein kinase II necessary for long-term potentiation and depression. , 1996, Journal of neurophysiology.

[29]  H. Schulman,et al.  Multifunctional Ca2+/calmodulin-dependent Protein Kinase Mediates Ca(2+)-induced , 2022 .

[30]  L Maler,et al.  The nucleus praeeminentialis: A Golgi study of a feedback center in the electrosensory system of gymnotid fish , 1983, The Journal of comparative neurology.

[31]  P. Greengard,et al.  Calcium/calmodulin-dependent protein kinase II increases glutamate and noradrenaline release from synaptosomes , 1990, Nature.

[32]  D W Tank,et al.  The role of presynaptic calcium in short-term enhancement at the hippocampal mossy fiber synapse , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[33]  Alcino J. Silva,et al.  The α-Ca2+/calmodulin kinase II: A bidirectional modulator of presynaptic plasticity , 1995, Neuron.

[34]  D. Benson,et al.  Alpha calcium/calmodulin-dependent protein kinase II selectively expressed in a subpopulation of excitatory neurons in monkey sensory- motor cortex: comparison with GAD-67 expression , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[35]  J. Blundon,et al.  Residual free calcium is not responsible for facilitation of neurotransmitter release. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[36]  H. Schulman,et al.  Neuronal Ca2+/calmodulin-dependent protein kinases. , 1992, Annual review of biochemistry.

[37]  Paul Greengard,et al.  Distinct pools of synaptic vesicles in neurotransmitter release , 1995, Nature.

[38]  M. Charlton,et al.  Homosynaptic facilitation of transmitter release in crayfish is not affected by mobile calcium chelators: implications for the residual ionized calcium hypothesis from electrophysiological and computational analyses. , 1994, Journal of neurophysiology.

[39]  M. Seagar,et al.  Developmental Regulation of Synaptotagmin I, II, III, and IV mRNAs in the Rat CNS , 1997, The Journal of Neuroscience.

[40]  Jixin Wang,et al.  Inactivation of the sarcoplasmic reticulum calcium channel by protein kinase , 1992, Nature.

[41]  L. Maler,et al.  The posterior lateral line lobe of certain gymnotoid fish: Quantitative light microscopy , 1979, The Journal of comparative neurology.

[42]  L. Maler,et al.  The cytology of the posterior lateral line lobe of high‐frequency weakly electric fish (gymnotidae): Dendritic differentiation and synaptic specificity in a simple cortex , 1981, The Journal of comparative neurology.

[43]  Lubert Stryer,et al.  Dual role of calmodulin in autophosphorylation of multifunctional cam kinase may underlie decoding of calcium signals , 1994, Neuron.

[44]  R. Zucker,et al.  Mitochondrial Involvement in Post-Tetanic Potentiation of Synaptic Transmission , 1997, Neuron.

[45]  P. Greengard,et al.  Calcium‐dependent serine phosphorylation of synaptophysin , 1993, Synapse.

[46]  R. Scheller,et al.  Phosphorylation of synaptic vesicle proteins: modulation of the alpha SNAP interaction with the core complex. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[47]  L. Maler,et al.  Correlating gamma‐aminobutyric acidergic circuits and sensory function in the electrosensory lateral line lobe of a gymnotiform fish , 1994, The Journal of comparative neurology.

[48]  H. Hidaka,et al.  Effect of a new Ca2(+)-calmodulin-dependent protein kinase II inhibitor on GABA release in cerebrospinal fluid of the rat. , 1990, Journal of Pharmacology and Experimental Therapeutics.

[49]  R. Zucker,et al.  Residual Ca2 + and short-term synaptic plasticity , 1994, Nature.

[50]  Paul Antoine Salin,et al.  Distinct short-term plasticity at two excitatory synapses in the hippocampus. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[51]  R. Tsien,et al.  Inhibition of postsynaptic PKC or CaMKII blocks induction but not expression of LTP. , 1989, Science.

[52]  M H Ellisman,et al.  Immunohistochemical localization of ryanodine binding proteins in the central nervous system of gymnotiform fish , 1992, The Journal of comparative neurology.

[53]  R. Nicoll,et al.  A role for protein kinases and phosphatases in the Ca2+-induced enhancement of hippocampal AMPA receptor-mediated synaptic responses , 1994, Neuron.

[54]  J. Bastian.  Gain control in the electrosensory system mediated by descending inputs to the electrosensory lateral line lobe , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[55]  H. Hidaka,et al.  Inhibition of voltage-gated Ca2+ channels and insulin secretion in HIT cells by the Ca2+/calmodulin-dependent protein kinase II inhibitor KN-62: comparison with antagonists of calmodulin and L-type Ca2+ channels. , 1992, Molecular pharmacology.

[56]  E R Kandel,et al.  Involvement of Pre- and Postsynaptic Mechanisms in Posttetanic Potentiation at Aplysia Synapses , 1997, Science.

[57]  T. Sudhof,et al.  Phosphorylation of rabphilin-3A by Ca2+/calmodulin- and cAMP-dependent protein kinases in vitro , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[58]  J Bastian.  Plasticity in an electrosensory system. II. Postsynaptic events associated with a dynamic sensory filter. , 1996, Journal of neurophysiology.

[59]  J. Suko,et al.  Phosphorylation of the purified cardiac ryanodine receptor by exogenous and endogenous protein kinases. , 1993, The Biochemical journal.

[60]  A. Nairn,et al.  Calcium/calmodulin-dependent protein kinase I. cDNA cloning and identification of autophosphorylation site. , 1993, The Journal of biological chemistry.

[61]  M H Ellisman,et al.  TTX-sensitive dendritic sodium channels underlie oscillatory discharge in a vertebrate sensory neuron , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[62]  K. Fukunaga,et al.  Ca2+/Calmodulin‐Dependent Protein Kinase II Inhibitor KN‐62 Inhibits Adrenal Medullary Chromaffin Cell Functions Independent of Its Action on the Kinase , 1996, Journal of neurochemistry.

[63]  W. Catterall,et al.  Phosphorylation of the Synaptic Protein Interaction Site on N-type Calcium Channels Inhibits Interactions with SNARE Proteins , 1997, The Journal of Neuroscience.

[64]  F Benfenati,et al.  Synaptic vesicle phosphoproteins and regulation of synaptic function. , 1993, Science.

[65]  L. Maler,et al.  Inositol 1,4,5‐trisphosphate receptor localization in the brain of a weakly electric fish (Apteronotus leptorhynchus) with emphasis on the electrosensory system , 1995, The Journal of comparative neurology.

[66]  N. Noguchi,et al.  Requirement of Calmodulindependent Protein Kinase II in Cyclic ADP-ribose-mediated Intracellular Ca2+ Mobilization (*) , 1995, The Journal of Biological Chemistry.

[67]  Y. Goda,et al.  SNAREs and regulated vesicle exocytosis. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[68]  R. Zucker,et al.  Exocytosis: A Molecular and Physiological Perspective , 1996, Neuron.