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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Apical maxi-K (K_Ca1.1) channels mediate K⁺ secretion by the mouse submandibular exocrine gland

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 (K_Ca1.1) but was unchanged in mice lacking the intermediate-conductance IK_Ca1 channel (K_Ca3.1). 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 K_Ca1.1 null mice, suggesting an important role for K_Ca1.1 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 K_Ca1.1 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 K_Ca1.1 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