Abstract
Transcellular Cl− secretion is, in general, mediated by two steps; (1) the entry step of Cl− into the cytosolic space from the basolateral space across the basolateral membrane by Cl− transporters, such as Na+-K+-2Cl− cotransporter (NKCC1, an isoform of NKCC), and (2) the releasing step of Cl− from the cytosolic space into the luminal (air) space across the apical membrane via Cl− channels, such as cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel. Transcellular Cl− secretion has been characterized by using various experimental techniques. For example, measurements of short-circuit currents in the Ussing chamber and patch clamp techniques provide us information on transepithelial ion movements via transcellular pathway, transepithelial conductance, activity (open probability) of single channel, and whole cell currents. Although many investigators have tried to clarify roles of Cl− channels and transporters located at the apical and basolateral membranes in transcellular Cl− secretion, it is still unclear how Cl− channels/transporters contribute to transcellular Cl− secretion and are regulated by various stimuli such as Ca2+ and cAMP. In the present study, we simulate transcellular Cl− secretion using mathematical models combined with electrophysiological measurements, providing information on contribution of Cl− channels/transporters to transcellular Cl− secretion, activity of electro-neutral ion transporters and how Cl− channels/transporters are regulated.
Highlights
Goblet cells located in airway surface epithelia and mucous cells of submucosal glands produce mucins, which are secreted into the airway space (Kim, 2012)
We tried to clarify how transcellular Cl− secretion varies in magnitude and time when the activity of Cl− channels and transporters located at the apical and basolateral membranes changes using mathematical simulation with three parameters: (1) the entry step of Cl− into the intracellular space from the basolateral space across the basolateral membrane by Cl− transporters, (2) the releasing step of Cl− from the intracellular space into the apical space across the apical membrane via Cl− channels, and (3) the releasing step of Cl− from the intracellular space to the basolateral space across the basolateral membrane via Cl− channels
This simulation method reported in the present study shows us how the activity of Cl− channels and transporters located at the apical and basolateral membranes contributes to the transcellular Cl− secretion, and the determination of the activity of electro-neutral Cl− transporter such as NKCC1
Summary
Goblet cells located in airway surface epithelia and mucous cells of submucosal glands produce mucins, which are secreted into the airway space (Kim, 2012). Using blockers of Cl− channels/transporters combined with the short-circuit current measurement technique, we can determine amounts of transepithelial Cl− secretion (Marunaka, 2014a; Sun et al, 2014a,b) Using this technique, we could not exactly determine how transcellular Cl− secretion varies in magnitude and time due to modification of activity of Cl− channels and transporters located at the apical and basolateral membranes. Data have been partly reported in abstract form (Sasamoto et al, 2014)
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