title: Activation of apical K+ conductances by muscarinic receptor stimulation in rat distal colon: fast and slow components.
abstract: In the epithelium of rat distal colon the acetylcholine analogue carbachol induces a transient increase of short-circuit current (Isc) via stimulation of cellular K+ conductances. Inhibition of the turnover of inositol-1,4,5-trisphosphate (IP3) by LiCl significantly reduced both the amplitude and the duration of this response. When the apical membrane was permeabilized with nystatin, LiCl nearly abolished the carbachol-induced activation of basolateral K+ conductances. In contrast, in epithelia, in which the basolateral membrane was bypassed by a basolateral depolarization, carbachol induced a biphasic increase in the K+ current across the apical membrane consisting of an early component carried by charybdotoxin- and tetraethylammonium-sensitive K+ channels followed by a sustained plateau carried by channels insensitive against these blockers. Only the latter was sensitive against LiCl or inhibition of protein kinases. In contrast, the stimulation of the early apical K+ conductance by carbachol proved to be resistant against inhibition of phospholipase C or protein kinases. However, apical dichlorobenzamil, an inhibitor of Na+/Ca2+ exchangers, or a Ca2+-free mucosal buffer solution significantly reduced the early component of the carbachol-induced apical K+ current. The presence of an apically localized Na+/Ca2+-exchanger was proven immunohistochemically. Taken together these experiments reveal divergent regulatory mechanisms for the stimulation of apical Ca2+-dependent K+ channels in this secretory epithelium, part of them being activated by an inflow of Ca2+ across the apical membrane.
authors.affiliation: Institut fùr Veterinär-Physiologie, Frankfurter Str. 100, D-35392 Giessen, Germany. gerhard.schultheiss@vetmed.uni-giessen.de
authors.forename: G
authors.initials: G
authors.lastname: Schultheiss
authors.forename: R
authors.initials: R
authors.lastname: Ribeiro
authors.forename: K H
authors.initials: KH
authors.lastname: Schäfer
authors.forename: M
authors.initials: M
authors.lastname: Diener
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D018679:Cholinergic Agonists / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000037:antagonists & inhibitors; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D007476:Ionophores / Q000494:pharmacology; D018021:Lithium Chloride / Q000494:pharmacology; D009761:Nystatin / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism*; D010738:Type C Phospholipases
chemical_list: D018679:Cholinergic Agonists; D007476:Ionophores; D024681:Potassium Channels, Calcium-Activated; D011976:Receptors, Muscarinic; C041470:3',4'-dichlorobenzamil; D009761:Nystatin; D000584:Amiloride; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D010738:Type C Phospholipases; D018021:Lithium Chloride