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ALIMENTARY |
1 Center for Oral Biology in the Aab Institute of Biomedical Sciences and Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
We have recently shown that the IK1 and maxi-K channels in parotid salivary gland acinar cells are encoded by the KCa3.1 and KCa1.1 genes, respectively, and in vivo stimulated parotid secretion is severely reduced in double-null mice. The current study tested whether submandibular acinar cell function also relies on these channels. We found that the K+ currents in submandibular acinar cells have the biophysical and pharmacological footprints of IK1 and maxi-K channels and their molecular identities were confirmed by the loss of these currents in KCa3.1- and KCa1.1-null mice. Unexpectedly, the pilocarpine-stimulated in vivo fluid secretion from submandibular glands was essentially normal in double-null mice. This result and the possibility of side-effects of pilocarpine on the nervous system, led us to develop an ex vivo fluid secretion assay. Fluid secretion from the ex vivo assay was substantially (about 75%) reduced in animals with both K+ channel genes ablated – strongly suggesting systemic complications with the in vivo assay. Additional experiments focusing on the membrane potential in isolated submandibular acinar cells revealed mechanistic details underlying fluid secretion in K+ channel-deficient mice. The membrane potential of submandibular acinar cells from wild-type mice remained strongly hyperpolarized (–55 ± 2 mV) relative to the Cl– equilibrium potential (–24 mV) during muscarinic stimulation. Similar hyperpolarizations were observed in KCa3.1- and KCa1.1-null mice (–51 ± 3 and –48 ± 3 mV, respectively), consistent with the normal fluid secretion produced ex vivo. In contrast, acinar cells from double KCa3.1/KCa1.1-null mice were only slightly hyperpolarized (–35 ± 2 mV) also consistent with the ex vivo (but not in vivo) results. Finally, we found that the modest hyperpolarization of cells from the double-null mice was maintained by the electrogenic Na+,K+-ATPase.
(Received 27 December 2006;
accepted after revision 16 March 2007;
first published online 22 March 2007)
Corresponding author J. E. Melvin: Center for Oral Biology, Medical Center Box 611, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA. Email: james_melvin{at}urmc.rochester.edu
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