Direct and remote modulation of l-channels in chromaffin cells: Distinct actions on α_1C and α_1D subunits?

Authors: Baldelli, Pietro¹; Hernández-Guijo, Jesus¹; Carabelli, Valentina¹; Novara, Monica¹; Cesetti, Tiziana¹; Andrés-Mateos, Eva²; Montiel, Carmen²; Carbone, Emilio³

Source: Molecular Neurobiology, Volume 29, Number 1, February 2004 , pp. 73-96(24)

Publisher: Humana Press

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Abstract:

Understanding precisely the functioning of voltage-gated Ca²⁺ channels and their modulation by signaling molecules will help clarifying the Ca²⁺-dependent mechanisms controlling exocytosis in chromaffin cells. In recent years, we have learned more about the various pathways through which Ca²⁺ channels can be up- or down-modulated by hormones and neurotransmitters and how these changes may condition chromaffin cell activity and catecolamine release. Recently, the attention has been focused on the modulation of L-channels (Cav 1), which represent the major Ca²⁺ current component in rat and human chromaffin cells. L-channels are effectively inhibited by the released content of secretory granules or by applying mixtures of exogenous ATP, opioids, and adrenaline through the activation of receptor-coupled G proteins. This unusual inhibition persists in a wide range of potentials and results from a direct (membrane-delimited) interaction of G protein subunits with the L-channels co-localized in membrane microareas. Inhibition of L-channels can be reversed when the cAMP/PKA pathway is activated by membrane permeable cAMP analog or when cells are exposed to isoprenaline (remote action), suggesting the existence of parallel and opposite effects on L-channel gating by distinctly activated membrane autoreceptors.

Here, the authors review the molecular components underlying these two opposing signaling pathways and present new evidence supporting the presence of two L-channel types in rat chromaffin cells (α_1C and α_1D), which open new interesting issues concerning Ca²⁺-channel modulation. In light of recent findings on the regulation of exocytosis by Ca²⁺-channel modulation, the authors explore the possible role of L-channels in the autocontrol of catecholamine release.

Document Type: Research article

DOI: http://dx.doi.org/10.1385/MN:29:1:73

Affiliations: 1: INFM Research Unit and Department of Neuroscience, Torino, Italy, 2: Department of Pharmacology, UAM, Madrid, Spain, 3: INFM Research Unit and Department of Neuroscience, Torino, Italy, Email: emilio.carbone@unito.it

Publication date: 2004-02-01