Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/3901
Title: | Regulation of Ca2+ influx by a protein kinase C activator in chromaffin cells: differential role of P/Q- and L-type Ca2+ channels | Authors: | Sena, Cristina M. Santos, Rosa M. Boarder, Michael R. Rosário, Luís M. |
Keywords: | Adrenal medulla chromaffin cell; Ca2+ concentration, cytosolic free; Phorbol ester; Protein kinase C; Ca2+ channel, voltage-sensitive | Issue Date: | 1999 | Citation: | European Journal of Pharmacology. 366:2-3 (1999) 281-292 | Abstract: | Phorbol esters reduce depolarization-evoked Ca2+ influx in adrenal chromaffin cells, suggesting that voltage-sensitive Ca2+ channels (VSCCs) are inhibited by protein kinase C-mediated phosphorylation. We now address the possibility that L- and P/Q-type Ca2+ channel subtypes might be differentially involved in phorbol ester action. In bovine chromaffin cells, short-term (10 min) incubations with phorbol 12-myristate 13-acetate (PMA) inhibited early high K+-evoked rises in cytosolic free Ca2+ concentration ([Ca2+]i) and the early component of the depolarization-evoked Mn2+ quenching of fura-2 fluorescence in a dose-dependent manner (IC50: 18 and 7 nM; maximal inhibitions: 45 and 48%, respectively). The protein kinase C inhibitor staurosporine (100 nM) reverted the inhibitory action of PMA. PMA (0.1-1 [mu]M) inhibited the early and late phases of the ionomycin (2 [mu]M)-evoked [Ca2+]i transients by 14-23%. [omega]-Agatoxin IVA, a blocker of P/Q-type Ca2+ channels, inhibited high K+-evoked [Ca2+]i rises in a dose-dependent fashion (IC50=50 nM). In contrast, 0.1 [mu]M [omega]-conotoxin GVIA, a blocker of N-type channels, was without effect. A sizeable (<45%) component of early Ca2+ influx persisted in the combined presence of [omega]-agatoxin IVA (100 nM) and nitrendipine (1 [mu]M). Simultaneous exposure to [omega]-agatoxin IVA and PMA inhibited both the early [Ca2+]i transients and Mn2+ quenching to a much greater extent than each drug separately. Inhibition of the [Ca2+]i transients by nitrendipine and PMA did not significantly exceed that produced by PMA alone. It is concluded that phorbol ester-mediated activation of protein kinase C inhibits preferentially L-type VSCCs over P/Q type channels in adrenal chromaffin cells. However, the possibility cannot be ruled out that dihydropyridine-resistant, non-P/Q type channels might also be negatively regulated by protein kinase C. This may represent an important pathway for the specific control of VSCCs by protein kinase C-linked receptors, not only in paraneurones but presumably also in neurones and other excitable cells. | URI: | https://hdl.handle.net/10316/3901 | DOI: | 10.1016/S0014-2999(98)00908-X | Rights: | openAccess |
Appears in Collections: | FCTUC Ciências da Vida - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
fileb49cc84bfa374c2f8701db3f424e8e29.pdf | 390.33 kB | Adobe PDF | View/Open |
SCOPUSTM
Citations
15
checked on May 1, 2023
WEB OF SCIENCETM
Citations
15
checked on May 2, 2023
Page view(s) 20
782
checked on Oct 16, 2024
Download(s)
318
checked on Oct 16, 2024
Google ScholarTM
Check
Altmetric
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.