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Am J Physiol Cell Physiol 294: C810-C819, 2008. First published January 23, 2008; doi:10.1152/ajpcell.00511.2007
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REPORT

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Apical maxi-K (KCa1.1) channels mediate K+ secretion by the mouse submandibular exocrine gland

Tetsuji Nakamoto,1 Victor G. Romanenko,1 Atsushi Takahashi,2 Ted Begenisich,1 and James E. Melvin1

1Center for Oral Biology and the Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York; and 2Clinics of Dentistry for the Disabled, Tohoku University Hospital, Sendai, Japan

Submitted 29 October 2007 ; accepted in final form 18 January 2008

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.

salivary gland; potassium secretion; calcium-activated K channels; duct cells



Address for reprint requests and other correspondence: J. E. Melvin, Center for Oral Biology, Univ. of Rochester Medical Center, Box 611, 601 Elmwood Ave., Rochester, NY 14642 (e-mail: james_melvin{at}urmc.rochester.edu)




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