Stimulation of Na⁺‐K⁺‐pump currents by epithelial nicotinic receptors in rat colon

Abstract

These results suggest a novel concept for the cholinergic regulation of transepithelial ion transport by costimulation of muscarinic and nicotinic epithelial receptors and a unique role of nicotinic receptors controlling the activity of the Na -K -ATPase.

Evidence for metabotropic function of epithelial nicotinic cholinergic receptors in rat colon

“…Nicotine (2·10 −4 mol·L −1 ), however, did not cause an increase in the SBFI ratio signal as one might expect, if nicotine would evoke an influx of Na + . The decrease in the SBFI signal is caused by a stimulation of the Na + -K + -pump as shown previously in Ussing chamber experiments (Bader et al, 2017). Not all cells responded to nicotine.…”

“…The ion transport mechanism, which is under the control of epithelial nicotinic receptors, is the basolateral Na + -K + -ATPase, and in contrast to the classical view on cholinergic induced secretion, the action of ACh seems to be mediated by a coactivation of both muscarinic receptors (controlling Ca 2+ -dependent ion channels) and nicotinic receptors (Bader, Lottig, & Diener, 2017). The ion transport mechanism, which is under the control of epithelial nicotinic receptors, is the basolateral Na + -K + -ATPase, and in contrast to the classical view on cholinergic induced secretion, the action of ACh seems to be mediated by a coactivation of both muscarinic receptors (controlling Ca 2+ -dependent ion channels) and nicotinic receptors (Bader, Lottig, & Diener, 2017).…”

“…Their activation by selective nicotinic receptor agonists evokes a strong secretion of chloride. The ion transport mechanism, which is under the control of epithelial nicotinic receptors, is the basolateral Na + -K + -ATPase, and in contrast to the classical view on cholinergic induced secretion, the action of ACh seems to be mediated by a coactivation of both muscarinic receptors (controlling Ca 2+ -dependent ion channels) and nicotinic receptors (Bader, Lottig, & Diener, 2017).…”

“…The epithelia were apically permeabilized with nystatin (100 μg·ml −1 ). In the absence of a K + gradient (i.e., in the absence of a driving force for K + flux across basolateral K channels), this I sc is a Na + -dependent current carried by the Na + -K + -ATPase (Bader et al, 2017), which slowly fades over time (Schultheiss & Diener, 1997). In the absence of a K + gradient (i.e., in the absence of a driving force for K + flux across basolateral K channels), this I sc is a Na + -dependent current carried by the Na + -K + -ATPase (Bader et al, 2017), which slowly fades over time (Schultheiss & Diener, 1997).…”

“…The Na + -K + -ATPase, which is activated after stimulation of epithelial nAChR in rat colon (Bader et al, 2017), is regulated by different intracellular second messenger pathways usually coupled to metabotropic receptors. PKC can stimulate this ATPase by phosphorylating its FXYD subunit (Poulsen, Morth, Egebjerg, & Nissen, 2010).…”