The immediately releasable pool of mouse chromaffin cell vesicles is coupled to P/Q-type calcium channels via the synaptic protein interaction site

• Published in: PloS one Vol. 8; no. 1; p. e54846
• Main Authors: Álvarez, Yanina D, Belingheri, Ana Verónica, Perez Bay, Andrés E, Javis, Scott E, Tedford, H William, Zamponi, Gerald, Marengo, Fernando D
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.01.2013; Public Library of Science (PLoS)
• Subjects: Adrenal glands; Animals; Binding sites; Biology; Brain research; Calcium; Calcium - metabolism; Calcium channels; Calcium channels (L-type); Calcium channels (P/Q-type); Calcium channels (voltage-gated); Calcium Channels, P-Type - metabolism; Calcium Channels, Q-Type - metabolism; Cells, Cultured; Channels; Chromaffin cells; Chromaffin Cells - metabolism; Coupling; Exocytosis; Exocytosis - physiology; Laboratory animals; Localization; Mice; Peptides; Pharmacology; Physiology; Proteins; Regulation; Secretory Vesicles - metabolism; Vesicles; New York; United States > US; Calgary Alberta Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0054846

It is generally accepted that the immediately releasable pool is a group of readily releasable vesicles that are closely associated with voltage dependent Ca(2+) channels. We have previously shown that exocytosis of this pool is specifically coupled to P/Q Ca(2+) current. Accordingly, in the present work we found that the Ca(2+) current flowing through P/Q-type Ca(2+) channels is 8 times more effective at inducing exocytosis in response to short stimuli than the current carried by L-type channels. To investigate the mechanism that underlies the coupling between the immediately releasable pool and P/Q-type channels we transiently expressed in mouse chromaffin cells peptides corresponding to the synaptic protein interaction site of Cav2.2 to competitively uncouple P/Q-type channels from the secretory vesicle release complex. This treatment reduced the efficiency of Ca(2+) current to induce exocytosis to similar values as direct inhibition of P/Q-type channels via ω-agatoxin-IVA. In addition, the same treatment markedly reduced immediately releasable pool exocytosis, but did not affect the exocytosis provoked by sustained electric or high K(+) stimulation. Together, our results indicate that the synaptic protein interaction site is a crucial factor for the establishment of the functional coupling between immediately releasable pool vesicles and P/Q-type Ca(2+) channels.