Characterization of the Electrogenic Secretory Response in the Porcine Colon following in vivo Challenge with Brachyspira hyodysenteriae and “Brachyspira hampsonii”

Abstract

The effects of Brachyspira hyodysenteriae and “Brachyspira hampsonii” infections on the agonist induced electrogenic secretion were assessed to determine their contribution to the pathophysiology of swine dysentery. Proximal, apex and distal sections of colon were compared in healthy and diseased purebred Yorkshire grower pigs in Ussing chambers. Activation of secretion via isoproterenol (adrenergic agonist), carbachol (cholinergic agonist) and forskolin / 3‐isobutyl‐1‐methylxanthine (IBMX) demonstrated a significantly decreased change in short‐circuit current (Isc) in infected pigs in all three sections of colon compared to control, confirming the previous observation that swine dysentery is not secretory in nature. Tissue resistances did not account for this difference, rather, it was attributed to a decrease in Cl− secretion as indicated by a significant decrease in bumentanide inhibitable short‐circuit current in infected animals. qRT‐PCR was conducted to determine if a decrease in gene transcript was responsible for the loss of Cl− secretory function. The major chloride transport proteins of the epithelium, such as the Cystic Fibrosis transmembrane conductance regulator (CFTR), Transmembrane member protein 16A (TMEM16A) and Na‐K‐Cl co‐transporter 1 (NKCC1) were compared between healthy and diseased animals in all three sections of colon. Inflammatory mediators were also assed to probe potential mechanism behind the transporter modulation. mRNA expression for these channels were determined to be elevated in the infected samples compared to controls. This suggests that these Brachyspira species reduce the Cl− secretory response by directly inhibiting Cl− channels or by inhibiting the translation of mRNA into protein.Support or Funding InformationNatural Sciences and Engineering Research Council (NSERC) 371364 / 2010 to MEL & Alberta Livestock and Meat Association (ALMA) 2013R054R to JCH, MEL & JEH