{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T03:51:09Z","timestamp":1790481069833,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2007,5,23]],"date-time":"2007-05-23T00:00:00Z","timestamp":1179878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:p>We have recently shown that the IK1 and maxi\u2010K channels in parotid salivary gland acinar cells are encoded by the <jats:italic>K<jats:sub>Ca<\/jats:sub>3.1<\/jats:italic> and <jats:italic>K<jats:sub>Ca<\/jats:sub>1.1<\/jats:italic> genes, respectively, and <jats:italic>in vivo<\/jats:italic> stimulated parotid secretion is severely reduced in double\u2010null mice. The current study tested whether submandibular acinar cell function also relies on these channels. We found that the K<jats:sup>+<\/jats:sup> currents in submandibular acinar cells have the biophysical and pharmacological footprints of IK1 and maxi\u2010K channels and their molecular identities were confirmed by the loss of these currents in <jats:italic>K<jats:sub>Ca<\/jats:sub>3.1\u2010<\/jats:italic> and <jats:italic>K<jats:sub>Ca<\/jats:sub>1.1<\/jats:italic>\u2010null mice. Unexpectedly, the pilocarpine\u2010stimulated <jats:italic>in vivo<\/jats:italic> fluid secretion from submandibular glands was essentially normal in double\u2010null mice. This result and the possibility of side\u2010effects of pilocarpine on the nervous system, led us to develop an <jats:italic>ex vivo<\/jats:italic> fluid secretion assay. Fluid secretion from the <jats:italic>ex vivo<\/jats:italic> assay was substantially (about 75%) reduced in animals with both K<jats:sup>+<\/jats:sup> channel genes ablated \u2013 strongly suggesting systemic complications with the <jats:italic>in vivo<\/jats:italic> assay. Additional experiments focusing on the membrane potential in isolated submandibular acinar cells revealed mechanistic details underlying fluid secretion in K<jats:sup>+<\/jats:sup> channel\u2010deficient mice. The membrane potential of submandibular acinar cells from wild\u2010type mice remained strongly hyperpolarized (\u221255 \u00b1 2 mV) relative to the Cl<jats:sup>\u2212<\/jats:sup> equilibrium potential (\u221224 mV) during muscarinic stimulation. Similar hyperpolarizations were observed in <jats:italic>K<jats:sub>Ca<\/jats:sub>3.1\u2010<\/jats:italic> and <jats:italic>K<jats:sub>Ca<\/jats:sub>1.1<\/jats:italic>\u2010null mice (\u221251 \u00b1 3 and \u221248 \u00b1 3 mV, respectively), consistent with the normal fluid secretion produced <jats:italic>ex vivo<\/jats:italic>. In contrast, acinar cells from double <jats:italic>K<jats:sub>Ca<\/jats:sub>3.1\/K<jats:sub>Ca<\/jats:sub>1.1<\/jats:italic>\u2010null mice were only slightly hyperpolarized (\u221235 \u00b1 2 mV) also consistent with the <jats:italic>ex vivo<\/jats:italic> (but not <jats:italic>in vivo<\/jats:italic>) results. Finally, we found that the modest hyperpolarization of cells from the double\u2010null mice was maintained by the electrogenic Na<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>\u2010ATPase.<\/jats:p>","DOI":"10.1113\/jphysiol.2006.127498","type":"journal-article","created":{"date-parts":[[2007,3,23]],"date-time":"2007-03-23T00:08:22Z","timestamp":1174608502000},"page":"801-817","source":"Crossref","is-referenced-by-count":77,"title":["Regulation of membrane potential and fluid secretion by Ca<sup>2+<\/sup>\u2010activated K<sup>+<\/sup> channels in mouse submandibular glands"],"prefix":"10.1113","volume":"581","author":[{"given":"Victor 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