Regulation of slowly activating potassium current (I-Ks) by secretin in rat pancreatic acinar cells

1. The secretagogue-activated K+ conductance is indispensable for the elect rogenic Cl- secretion in exocrine tissue. In this study, we investigated th e effect of secretin and other cAMP-mediated secretagogues on the slowly ac tivating voltage-dependent K+ current (I-Ks) of rat pancreatic acinar cells (RPAs) with the whole-cell patch clamp technique. 2. Upon depolarization, RPAs showed I-Ks superimposed upon the instantaneou s background outward current. Secretin (5 nM), vasoactive intestinal peptid e (5 nM), forskolin (5 muM), isoprenaline (10 muM) or 3-isobutyl-1-methylxa nthine (IBMX, 0.1 mM) increased the amplitude of I-Ks two- to fourfold. 3. The physiological concentration of secretin (50 pM) had a relatively wea k effect on I-Ks (160% increase), which was significantly enhanced by trans ient co-stimulation with carbachol (CCh) (10 muM). However, the secretin-in duced 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 I-Ks channel is a common target for bot h Ca2+ and cAMP agonists. The vagal stimulation under the physiological con centration of secretin facilitates I-Ks, which provides an additional drivi ng force for Cl- secretion.