Nicotinic acetylcholine receptors of adrenal chromaffin cells

• Published in: Acta Physiologica 2008-02, Vol.192 (2), p.203-212
• Main Authors: Sala, F, Nistri, A, Criado, M
• Format: Article
• Language: English
• Subjects: Acetylcholine - metabolism; adrenal medulla; Animals; Biological and medical sciences; Cells, Cultured; cholinergic transmission; Chromaffin Cells - metabolism; desensitization; Fundamental and applied biological sciences. Psychology; Humans; Models, Biological; Neuronal Plasticity - physiology; nicotine; Nicotine - metabolism; receptor plasticity; Receptors, Nicotinic - metabolism; transcriptional regulation; Up-Regulation; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 1748-1708; 1748-1716
• DOI: 10.1111/j.1748-1716.2007.01804.x

In the adrenal medulla, acetylcholine released by the sympathetic splanchnic nerves activates neuronal-type nicotinic acetylcholine receptors (nAChRs) on the membrane of chromaffin cells which liberate catecholamines into the bloodstream in preparation for the fight and flight reactions. On adrenal chromaffin cells the main class of nAChRs is a pentameric assembly of α3 and β4 subunits that forms ion channels which produce membrane depolarization by increasing Na⁺, K⁺ and Ca²⁺ permeability. Homomeric α7 nicotinic receptors are expressed in a species-dependent manner and do not contribute to catecholamine secretion. Chromaffin cell nAChRs rapidly activate and desensitize with full recovery on washout. nAChR activity is subjected to various types of dynamic regulation. It is allosterically modulated by the endogenous neuropeptide substance P that stabilizes receptors in their desensitized state, thus depressing their responsiveness. The full-length peptide CGRP acts as a negative allosteric modulator by inhibiting responses without changing desensitization, whereas its N-terminal fragments act as positive allosteric modulators to transiently enhance nAChR function. nAChR expression increases when cells are chronically exposed to either selective antagonists or agonists such as nicotine, a protocol mimicking the condition of chronic heavy smokers. In this case, large upregulation of nAChRs occurs even though most of the extra nAChRs remain inside the cells, creating a mismatch between the increase in total nAChRs and increase in functional nAChRs on the cell surface. These findings highlight the plastic properties of cholinergic neurotransmission in the adrenal medulla to provide robust mechanisms for adapting catecholamine release to acute and chronic changes in sympathetic activity.