Compensatory increase in P/Q-calcium current-mediated synaptic transmission following chronic block of N-type channels.
Synaptic transmission is triggered by presynaptic calcium influx through voltage-gated calcium channels. Axon terminals of central neurons express a diverse set of homologous calcium channels, giving rise to P/Q-, N-, and R-type calcium currents. The relative contribution of these components to presynaptic calcium signalling is heterogeneous and incompletely understood. Here we report that chronic block of N-type calcium channels in developing cultured rat hippocampal neurons leads to a compensatory up-regulation of P/Q-type calcium currents. This increase was measured directly by recording whole-cell calcium currents as well as in spontaneous inhibitory postsynaptic currents, indicating a global functional up-regulation of the P/Q-component. In contrast, immunocytochemical stainings as well as quantitative real-time PCR analysis did not reveal an increased expression of Ca(v) 2.1, the underlying calcium channel alpha-subunit. We conclude that developing hippocampal neurons can compensate for the loss of one calcium current component by up-regulation of alternative isoforms at the post-translational level.
Grimm
Christiane
C
Department of Physiology and Pathophysiology, University of Heidelberg, INF 326, 69120 Heidelberg, Germany.
Holter
Nadine I
NI
Draguhn
Andreas
A
Bruehl
Claus
C
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism*; D020865:Calcium Channels, P-Type / Q000378:metabolism*; D020907:Calcium Channels, Q-Type / Q000378:metabolism*; D002478:Cells, Cultured; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009435:Synaptic Transmission / Q000502:physiology*; D020960:omega-Conotoxins / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D020960:omega-Conotoxins; C078452:ziconotide