Regulation of slowly activating potassium current (IKs) by secretin in rat pancreatic acinar cells

Abstract

1. The secretagogue-activated K+ conductance is indispensable for the electrogenic Cl-secretion in exocrine tissue. In this study, we investigated the effect of secretin and other cAMP-mediated secretagogues on the slowly activating voltage-dependent K+ current (IKs) of rat pancreatic acinar cells (RPAs) with the whole-cell patch clamp technique. 2. Upon depolarization, RPAs showed IKs superimposed upon the instantaneous background outward current. Secretin (5 nM), vasoactive intestinal peptide (5 nM), forskolin (5 μM), isoprenaline (10 μM) or 3-isobutyl-1-methylxanthine (IBMX, 0.1 mM) increased the amplitude of IKs two- to fourfold. 3. The physiological concentration of secretin (50 pM) had a relatively weak effect on IKs (160% increase), which was significantly enhanced by transient co-stimulation with carbachol (CCh) (10 μM). However, the secretin-induced production of cAMP, which was measured by enzyme-linked immunosorbent assay, was not augmented by co-stimulation with CCh. 4. This study is the first to demonstrate the regulation of K+ channels in RPAs by cAMP-mediated agonists. The IKs channel is a common target for both Ca2+ and cAMP agonists. The vagal stimulation under the physiological concentration of secretin facilitates IKs, which provides an additional driving force for Cl- secretion.