Metabolism and trafficking of N-type voltage-operated calcium channels in neurosecretory cells.
The N-type voltage-operated calcium channel has been characterized over the years as a high-threshold channel, with variable inactivation kinetics, and a unique ability to bind with high affinity and specificity omega-conotoxin GVIA and related toxins. This channel is particularly expressed in some neurons and endocrine cells, where it participates in several calcium-dependent processes, including secretion. Omega-conotoxin GVIA was instrumental not only for the biophysical and pharmacological characterization of N-type channels but also for the development of in vitro assays for studying N-type VOCC subcellular localization, biosynthesis, turnover, as well as short-and long-term regulation of its expression. We here summarize our studies on N-type VOCC expression in neurosecretory cells, with a major emphasis on recent data demonstrating the presence of N-type channels in intracellular secretory organelles and their recruitment to the cell surface during regulated exocytosis.
CNR Center of Cellular and Molecular Pharmacology, Department of Medical Pharmacology, University of Milan, Italy.
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Sher
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Rosa
M
M
Francolini
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A
Codignola
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E
Morlacchi
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E
Taverna
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F
Giovannini
A
A
Brioschi
F
F
Clementi
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McEnery
M
M
Passafaro
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020864:Calcium Channels, N-Type; D020013:Calcium Signaling / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D008564:Membrane Potentials; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism*; D009490:Neurosecretory Systems / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells / Q000378:metabolism; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D015854:Up-Regulation; D020866:omega-Conotoxin GVIA
D002118:Calcium; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D009419:Nerve Tissue Proteins; D010455:Peptides; D020866:omega-Conotoxin GVIA; C053157:omega-conotoxin receptor