KvLQT1, a newly found subfamily of K+ channel protein, distributes widely in the excretory epithelial cell membrane including rat pancreatic acini. For exocrine secretion of Cl- and water by muscarinic stimulation, concomitant activation of K+ channels is necessary. In rodent pancreatic acini, however, the carbachol (CCh)-activated K+ channel was poorly investigated. Here, in rat pancreatic acini, we characterized the voltage-dependent, slowly activating outward current (IKs) that was augmented by CCh. Intact acini were obtained by enzymatic digestion and the whole-cell patch clamp was applied. A step-like depolarization from -60 to 0 mV induces IKs superimposed upon the instantaneous background current. CCh (10 μM) which is known to activate Cl- channels via a Ca2+-mediated pathway, sharply depolarized the membrane. By washout of CCh and decrease of inward current, persistent augmentation of IKs was revealed by the same step-pulse protocol. Since the very slow kinetics of IKs (>2 sec for full activation) suggested an involvement of KVLQT1+KCNE1 complex-type K+ channel, we tested the known blockers of KVLQT1. A chromanol 293B potently blocked both the IKs (IC50 = 3 μM) and Ba+ was a poor inhibitor (IC50 = 3 mM). The addition of 293B further depolarized the membrane in the presence of CCh. These data suggest the presence of IKs channels in rat pancreatic acini and their muscarinic regulation. Not only the Ca2+-mediated but also the cAMP-mediated secretagogues could augment the amplitude of IKs in the pancreatic acini. Secretin (5 nM), VIP (5 nM), forskolin (5 μM), isoprenaline (10 μM) or IBMX (0.1 mM) increased the amplitude of IKs two to four fold. 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 CCh. This study demonstrates that IKs channel is a common target for both Ca2+- and cAMP-agonists in the pancreatic acini. The immunofluorescence microscopy study of the pancreatic acini from KCNE1 knock-out mice suggested that the membrane translocation of KvLQT1 is related with the expression of KCNE1.
Source: Korean Journal of Physiology & Pharmacology.2000 Oct;4(Suppl):S6-S6
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