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.
Sher
E
E
CNR Center of Cellular and Molecular Pharmacology, Department of Medical Pharmacology, University of Milan, Italy.
Rosa
P
P
Francolini
M
M
Codignola
A
A
Morlacchi
E
E
Taverna
E
E
Giovannini
F
F
Brioschi
A
A
Clementi
F
F
McEnery
M W
MW
Passafaro
M
M
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