Altered adrenal chromaffin cell function during experimental colitis

Area of Science:

• Neuroscience
• Physiology
• Gastroenterology

Background:

• The sympathetic nervous system regulates visceral functions via catecholamine release from sympathetic neurons and adrenal chromaffin cells (ACCs).
• Previous research indicated reduced norepinephrine secretion in experimental colitis due to inhibited voltage-gated calcium currents (I(Ca)) in sympathetic neurons.

Purpose of the Study:

• To investigate if colonic inflammation similarly impairs depolarization-induced calcium influx in ACCs.
• To assess alterations in ACC function during experimental colitis models.

Main Methods:

• Utilized the dextran sulfate sodium (DSS) model for acute colitis in mice.
• Employed fura 2-acetoxymethyl ester calcium imaging and perforated patch-clamp electrophysiology to assess ACC function.
• Examined ACCs from mice with DSS-induced acute colitis, 2,4,6-trinitrobenzene sulfonic acid-induced acute colitis, and DSS-induced chronic colitis.

Main Results:

• DSS-induced acute colitis significantly reduced high-K(+)-stimulated intracellular calcium concentration ([Ca(2+)](i)) in ACCs to 74% of control levels.
• Acute colitis led to ACC hyperpolarization and enhanced delayed-rectifier K(+) and voltage-gated Na(+) currents.
• Importantly, I(Ca) was significantly inhibited in ACCs from colitis models, with peak I(Ca) density reduced to 61% in the DSS acute colitis model.

Conclusions:

• Colitis impairs voltage-dependent calcium influx in adrenal chromaffin cells.
• Altered calcium signaling in ACCs during colitis may decrease systemic catecholamine levels.
• These findings demonstrate aberrant ACC function during experimental colitis, potentially significant for inflammatory bowel disease pathogenesis.