title: Apical maxi-K (KCa1.1) channels mediate K+ secretion by the mouse submandibular exocrine gland.
abstract: The exocrine salivary glands of mammals secrete K+ by an unknown pathway that has been associated with HCO3(-) efflux. However, the present studies found that K+ secretion in the mouse submandibular gland did not require HCO3(-), demonstrating that neither K+/HCO3(-) cotransport nor K+/H+ exchange mechanisms were involved. Because HCO3(-) did not appear to participate in this process, we tested whether a K channel is required. Indeed, K+ secretion was inhibited >75% in mice with a null mutation in the maxi-K, Ca2+-activated K channel (KCa1.1) but was unchanged in mice lacking the intermediate-conductance IKCa1 channel (KCa3.1). Moreover, paxilline, a specific maxi-K channel blocker, dramatically reduced the K+ concentration in submandibular saliva. The K+ concentration of saliva is well known to be flow rate dependent, the K+ concentration increasing as the flow decreases. The flow rate dependence of K+ secretion was nearly eliminated in KCa1.1 null mice, suggesting an important role for KCa1.1 channels in this process as well. Importantly, a maxi-K-like current had not been previously detected in duct cells, the theoretical site of K+ secretion, but we found that KCa1.1 channels localized to the apical membranes of both striated and excretory duct cells, but not granular duct cells, using immunohistochemistry. Consistent with this latter observation, maxi-K currents were not detected in granular duct cells. Taken together, these results demonstrate that the secretion of K+ requires and is likely mediated by KCa1.1 potassium channels localized to the apical membranes of striated and excretory duct cells in the mouse submandibular exocrine gland.
authors.affiliation: Center for Oral Biology, Department of Pharmacology and Physiology, Univ. of Rochester Medical Center, Box 611, 601 Elmwood Ave, Rochester, NY 14642, USA.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Nakamoto
authors.forename: Victor G
authors.initials: VG
authors.lastname: Romanenko
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Ted
authors.initials: T
authors.lastname: Begenisich
authors.forename: James E
authors.initials: JE
authors.lastname: Melvin
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D007211:Indoles / Q000494:pharmacology; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism; D015640:Ion Channel Gating; D007700:Kinetics; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012463:Saliva / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013363:Submandibular Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001639:Bicarbonates; D007211:Indoles; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C465449:Kcnma1 protein, mouse; C496925:Kcnn4 protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D026902:Potassium Channel Blockers; C048220:paxilline; D012964:Sodium; D011188:Potassium