title: Altered adrenal chromaffin cell function during experimental colitis.
abstract: The sympathetic nervous system regulates visceral function through the release of catecholamines and cotransmitters from postganglionic sympathetic neurons and adrenal chromaffin cells (ACCs). Previous studies have shown that norepinephrine secretion is decreased during experimental colitis due to the inhibition of voltage-gated Ca(2+) current (I(Ca)) in postganglionic sympathetic neurons. The present study examined whether colonic inflammation causes a similar impairment in depolarization-induced Ca(2+) influx in ACCs using the dextran sulfate sodium (DSS) model of acute colitis in mice. Alterations in ACC function during colitis were assessed using fura 2-acetoxymethyl ester Ca(2+) imaging techniques and perforated patch-clamp electrophysiology. In ACCs isolated from mice with DSS-induced acute colitis, the high-K(+)-stimulated increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) was significantly reduced to 74% of the response of ACCs from control mice. Acute colitis caused a 10-mV hyperpolarization of ACC resting membrane potential, without a significant effect on cellular excitability. Delayed-rectifier K(+) and voltage-gated Na(+) current densities were significantly enhanced in ACCs from mice with DSS-induced acute colitis, with peak current densities of 154 and 144% that of controls, respectively. Importantly, acute colitis significantly inhibited I(Ca) in ACCs between -25 and +20 mV. Peak I(Ca) density in ACCs from mice with DSS-induced acute colitis was 61% that of controls. High-K(+)-induced increases in [Ca(2+)](i) were also reduced in ACCs from mice with 2,4,6-trinitrobenzene sulfonic acid-induced acute colitis and DSS-induced chronic colitis to 68 and 78% of the control responses, respectively. Our results suggest that, during colitis, voltage-dependent Ca(2+) influx is impaired in ACCs. Given the importance of Ca(2+) signaling in exocytosis, these alterations may decrease systemic catecholamine levels, which could play an important role in inflammatory bowel disease. This is the first demonstration of aberrant ACC function during experimental colitis.
authors.affiliation: Department of Physiology, Gastrointestinal Diseases Research Unit, Centre for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada.
authors.forename: Mark K
authors.initials: MK
authors.lastname: Lukewich
authors.forename: Alan E
authors.initials: AE
authors.lastname: Lomax
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D019439:Chromaffin Cells / Q000502:physiology*; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D016264:Dextran Sulfate; D004594:Electrophysiology; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015220:Calcium Channels; D016264:Dextran Sulfate; D009195:Peroxidase; D002118:Calcium