ABSTRACT
Tetraethylammonium (TEA) induces a form of long-term potentiation (LTP) that is independent on N-methyl-D-aspartate (NMDA) receptor activation (LTP(K)). LTP(K) may be a suitable chemical model to study molecular mechanisms underlying LTP. We monitored the phosphorylation state of two identified neural-specific protein kinase C (PKC) substrates (the presynaptic protein GAP-43/B-50 and postsynaptic protein RC3) after different chemical depolarisations. TEA induced a long-lasting increase in synaptic efficacy in the CA1 field of the hippocampus and increased the phosphorylation of both GAP-43/B-50 and RC3 (51 and 56.1%, respectively). These effects were blocked by the voltage-dependent calcium channel antagonist nifedipine, but not by the NMDA receptor antagonist AP5. These data show that in LTP(K) the in situ phosphorylation of pre-and postsynaptic PKC substrates is increased, indicating that NMDA receptor-dependent and NMDA receptor-independent LTP share common Ca(2+)-dependent expression mechanisms, including activation of pre- and postsynaptic PKC.
Subject(s)
Hippocampus/drug effects , Hippocampus/metabolism , Long-Term Potentiation/drug effects , Long-Term Potentiation/physiology , Presynaptic Terminals/drug effects , Presynaptic Terminals/metabolism , Protein Kinase C/drug effects , Protein Kinase C/metabolism , Synaptic Membranes/drug effects , Synaptic Membranes/metabolism , Tetraethylammonium/pharmacology , 2-Amino-5-phosphonovalerate/pharmacology , 4-Aminopyridine/pharmacology , Animals , Calcium Channel Blockers/pharmacology , Calmodulin-Binding Proteins/metabolism , Excitatory Amino Acid Antagonists/pharmacology , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , GAP-43 Protein/metabolism , Hippocampus/cytology , In Vitro Techniques , Nerve Tissue Proteins/metabolism , Neurogranin , Nifedipine/pharmacology , Phosphorylation , Potassium Channel Blockers , Potassium Channels/drug effects , Potassium Channels/metabolism , Presynaptic Terminals/ultrastructure , Rats , Signal Transduction/drug effects , Signal Transduction/physiology , Synaptic Membranes/ultrastructure , Synaptic Transmission/drug effects , Synaptic Transmission/physiologyABSTRACT
Jak3, a member of the Janus tyrosine kinase family is an intracellular kinase functionally coupled to cytokine receptors that share a common gamma chain (gamma c). Defects in the gamma c or Jak3 result in T-B + severe combined immunodeficiency (SCID). In order to clarify discrepancies between earlier reported genomic organisations of human JAK3, the present study was undertaken to redefine its whole exon-intron structure. The genomic structure of human JAK3 consists of 23 exons and 22 introns, and shows strong homology with the organisation of the murine JAK3 locus. The exon-intron sequences provided in this report can be used to facilitate the identification of new Jak3-deficient SCID patients, including prenatal diagnosis.
