Molecular Identification and Physiological Roles of Parotid Acinar Cell Maxi-K Channels

The physiological success of fluid-secreting tissues relies on a regulated interplay between Ca2+-activated Cl– and K+ channels. Parotid acinar cells express two types of Ca2+-activated K+ channels: intermediate conductance IK1 channels and maxi-K channels. The IK1 channel is encoded by the KCa3.1 gene, and the KCa1.1 gene is a likely candidate for the maxi-K channel. To confirm the genetic identity of the maxi-K channel and to probe its specific roles, we studied parotid glands in mice with the KCa1.1 gene ablated. Parotid acinar cells from these animals lacked maxi-K channels, confirming their genetic identity. The stimulated parotid gland fluid secretion rate was normal, but the sodium and potassium content of the secreted fluid was altered. In addition, we found that the regulatory volume decrease in acinar cells was substantially impaired in KCa1.1-null animals. We examined fluid secretion from animals with both K+ channel genes deleted. The secretion rate was severely reduced, and the ion content of the secreted fluid was significantly changed. We measured the membrane potentials of acinar cells from wild-type mice and from animals with either or both K+ channel genes ablated. They revealed that the observed functional effects on fluid secretion reflected alterations in cell membrane voltage. Our findings show that the maxi-K channels are critical for the regulatory volume decrease in these cells and that they play an important role in the sodium uptake and potassium secretion process in the ducts of these fluid-secreting salivary glands. The physiological success of fluid-secreting tissues relies on a regulated interplay between Ca2+-activated Cl– and K+ channels. Parotid acinar cells express two types of Ca2+-activated K+ channels: intermediate conductance IK1 channels and maxi-K channels. The IK1 channel is encoded by the KCa3.1 gene, and the KCa1.1 gene is a likely candidate for the maxi-K channel. To confirm the genetic identity of the maxi-K channel and to probe its specific roles, we studied parotid glands in mice with the KCa1.1 gene ablated. Parotid acinar cells from these animals lacked maxi-K channels, confirming their genetic identity. The stimulated parotid gland fluid secretion rate was normal, but the sodium and potassium content of the secreted fluid was altered. In addition, we found that the regulatory volume decrease in acinar cells was substantially impaired in KCa1.1-null animals. We examined fluid secretion from animals with both K+ channel genes deleted. The secretion rate was severely reduced, and the ion content of the secreted fluid was significantly changed. We measured the membrane potentials of acinar cells from wild-type mice and from animals with either or both K+ channel genes ablated. They revealed that the observed functional effects on fluid secretion reflected alterations in cell membrane voltage. Our findings show that the maxi-K channels are critical for the regulatory volume decrease in these cells and that they play an important role in the sodium uptake and potassium secretion process in the ducts of these fluid-secreting salivary glands. In salivary glands, as in other secretory epithelia, muscarinic stimulation increases intracellular Ca2+, which activates the anion channels that drive fluid secretion. The activated anion channels allow an efflux of Cl– ions from the acinar cells into the lumen of the gland. This Cl– efflux generates a lumen negative voltage gradient sufficient to drive sodium ions into the lumen via a paracellular pathway. The net result is the secretion of sodium and chloride, with water following osmotically. For the fluid secretion process to be sustained, an apical cell driving force for Cl– efflux must be maintained. This is accomplished by the hyperpolarizing influence of acinar cell K+ channels activated by intracellular Ca2+ (1Petersen O.H. Maruyama Y. Nature. 1984; 307: 693-696Crossref PubMed Scopus (476) Google Scholar). Two types of Ca2+-activated K+ channels are expressed in parotid acinar cells: a voltage-independent channel of “intermediate” single channel conductance (IK1) and a large conductance K+ channel (maxi-K) that is gated by voltage as well as by Ca2+ (2Maruyama Y. Nishiyama A. Teshima T. Jpn. J. Physiol. 1986; 36: 219-223Crossref PubMed Scopus (10) Google Scholar, 3Wegman E.A. Ishikawa T. Young J.A. Cook D.I. Am. J. Physiol. 1992; 263: G786-G794PubMed Google Scholar, 4Ishikawa T. Murakami M. Seo Y. Pfluegers Arch. Eur. J. Physiol. 1994; 428: 516-525Crossref PubMed Scopus (23) Google Scholar, 5Park K. Case R.M. Brown P.D. Arch. Oral Biol. 2001; 46: 801-810Crossref PubMed Scopus (24) Google Scholar, 6Takahata T. Hayashi M. Ishikawa T. Am. J. Physiol. 2003; 284: C127-C144Crossref PubMed Google Scholar). In addition to their biophysical properties, these two types of channels can be distinguished by their pharmacological footprints. For example, IK1 channels are specifically inhibited by clotrimazole (7Ishii T.M. Silvia C. Hirschberg B. Bond C.T. Adelman J.P. Maylie J. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 11651-11656Crossref PubMed Scopus (515) Google Scholar, 8Logsdon N.J. Kang J. Togo J.A. Christian E.P. Aiyar J. J. Biol. Chem. 1997; 272: 32723-32726Abstract Full Text Full Text PDF PubMed Scopus (256) Google Scholar) and maxi-K channels by paxilline (9Gribkoff V.K. Starrett Jr., J.E. Dworetzky S.I. Adv. Pharmacol. 1997; 37: 319-348Crossref PubMed Scopus (88) Google Scholar). A PCR screen of mouse parotid acinar cells revealed two candidate genes for encoding these two K+ channels: KCa1.1 (also know as Kcnma1) and KCa3.1 (Kcnn4) (10Nehrke K. Quinn C.C. Begenisich T. Am. J. Physiol. 2003; 284: C535-C546Crossref PubMed Scopus (56) Google Scholar). Heterologous expression of these two genes produces channels with the biophysical and pharmacological profiles of the native maxi-K and IK1 channels (10Nehrke K. Quinn C.C. Begenisich T. Am. J. Physiol. 2003; 284: C535-C546Crossref PubMed Scopus (56) Google Scholar). Although these results provide strong circumstantial evidence for the genetic identification of the parotid K+ channels, gene ablation studies would be definitive and help to uncover the physiological roles of these channels. Ablation of the KCa3.1 gene eliminates expression of IK1 channels, confirming the molecular identity of the IK1 channel (11Begenisich T. Nakamoto T. Ovitt C.E. Nehrke K. Brugnara C. Alper S.L. Melvin J.E. J. Biol. Chem. 2004; 279: 47681-47687Abstract Full Text Full Text PDF PubMed Scopus (167) Google Scholar). However, parotid fluid secretion from KCa3.1(–/–) mice is normal, perhaps because the remaining maxi-K channels are sufficient to maintain the necessary Cl– driving force and, hence, fluid secretion. In addition to their ability to regulate fluid secretion, parotid acinar cells, like many other cells, also dynamically regulate their cell volume: a decrease in extracellular osmolality causes the cells to swell, as expected, but also activates K+ and Cl– channels. The resulting efflux of these ions reduces cell volume to near the initial resting value. The ion channels responsible for this regulatory volume decrease (RVD) 3The abbreviations used are: RVD, regulatory volume decrease; BAPTA, 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid; CCh, carbachol; pF, picofarads. generally include both K+ and Cl– channels, but the specific types vary among different cells (reviewed in Ref. 12Wehner F. Olsen H. Tinel H. Kinne-Saffran E. Kinne R.K. Rev. Physiol. Biochem. Pharmacol. 2003; 148: 1-80Crossref PubMed Scopus (314) Google Scholar). The molecular identity of the K+ channels involved in is for cell For example, IK1 channels by the KCa3.1 are for and (11Begenisich T. Nakamoto T. Ovitt C.E. Nehrke K. Brugnara C. Alper S.L. Melvin J.E. J. Biol. Chem. 2004; 279: 47681-47687Abstract Full Text Full Text PDF PubMed Scopus (167) Google and maxi-K channels in in cells Brown P.D. J. Biol. 1994; PubMed Scopus Google cells M. S. J. Biol. PubMed Scopus Google and a cell M. A. E. Am. J. Physiol. PubMed Scopus Google Scholar). The channels for in parotid acinar cells are Ablation of the KCa3.1 gene on in parotid acinar of maxi-K channels by the specific paxilline substantially RVD, that this channel is for in these cells (11Begenisich T. Nakamoto T. Ovitt C.E. Nehrke K. Brugnara C. Alper S.L. Melvin J.E. J. Biol. Chem. 2004; 279: 47681-47687Abstract Full Text Full Text PDF PubMed Scopus (167) Google Scholar). gene ablation studies that KCa3.1 the IK1 channel and that KCa3.1(–/–) mice parotid gland fluid secretion and in their parotid acinar To confirm the molecular identity of the maxi-K channel and to probe its physiological roles, we studied mice in which the KCa1.1 gene was J. Biol. Chem. 2004; 279: Full Text Full Text PDF PubMed Scopus Google Scholar). Parotid acinar cells from these animals lacked the and Ca2+-activated maxi-K channel confirming that these channels are encoded by the KCa1.1 fluid secretion from the parotid glands of these animals was normal, but in the sodium and potassium content of the secreted in KCa1.1-null mice was substantially secretion from animals with both K+ channel genes was severely and by large alterations in the ion content of the secreted The functional effects on fluid secretion from the animals well with alterations in parotid acinar cell membrane results the physiological roles of the Ca2+-activated K+ channels in fluid-secreting salivary glands. of mice with or Ca2+-activated K+ channel genes deleted. The mice J. Biol. Chem. 2004; 279: Full Text Full Text PDF PubMed Scopus Google Scholar) a from Our of KCa3.1(–/–) mice (11Begenisich T. Nakamoto T. Ovitt C.E. Nehrke K. Brugnara C. Alper S.L. Melvin J.E. J. Biol. Chem. 2004; 279: 47681-47687Abstract Full Text Full Text PDF PubMed Scopus (167) Google Scholar) and on a animals used in on KCa3.1(–/–) and mice and wild-type of the mice by both and wild-type on a genetic of and animals for on mice wild-type on this cells by as we (10Nehrke K. Quinn C.C. Begenisich T. Am. J. Physiol. 2003; 284: C535-C546Crossref PubMed Scopus (56) Google Scholar) with In mice by to and by via The parotid glands in and Parotid was with in and for by by with and To single cells, the was in and for and as in the of cell volume we the by K. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google and of of this by Melvin J.E. J.E. T. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). acinar cells with in and for and to a on the of a and with physiological sodium and with The was by a volume of water to this The was on an with a and of the was the and volume expressed as a of the to the in In by of to the ducts from the and parotid glands a The was and to a the was a regulated The of the ducts into was stimulated by of was for and the of the parotid glands and of a parotid the mice by The rate was to gland and expressed as of gland and potassium by was measured an ion osmolality was with a glands from and and the was in was from of the to the of was to by on an The was by on and on membrane with for and with the by PCR and and The was used to probe was by PCR parotid and the following and the and with are on and and The KCa1.1 was to for The membrane was with and with and the was with the KCa1.1 cell voltage with an was a by a K+ channel with in which of the Cl– was with the The of sodium potassium and The potassium and which a Ca2+ of Biol. 1994; PubMed Scopus Google also The measured in these was that to membrane voltage was Parotid acinar cell membrane potentials measured with the of an a was used for the A. J. Physiol. PubMed Scopus Google Scholar) with an and The with a of potassium BAPTA, and and with the and the was used as an of the of the cell membrane the was by with an from cells in which the was from the cell For these the was with the and with the in this the voltage was a the was with the this be an in We hyperpolarizing of measured the resulting in membrane and the membrane via a and The membrane with the voltage with and The and between and with the to cell as cell of the cells stimulated with with membrane potentials and the The membrane voltage was the initial and the of the The membrane potentials of resting cells and the that in a are as the between by with with and we both the of and the of are or in the as Ca2+-activated K+ in Parotid in the parotid acinar cells express two types of Ca2+-activated K+ channels: the and voltage-independent IK1 channel and a maxi-K channel that is gated by voltage as well as by We that expressed KCa3.1 channels biophysical and pharmacological that are from of native parotid IK1 channels and that ablation of the KCa3.1 gene eliminates the IK1 channel from the parotid cells, maxi-K channels (10Nehrke K. Quinn C.C. Begenisich T. Am. J. Physiol. 2003; 284: C535-C546Crossref PubMed Scopus (56) Google Scholar, T. Nakamoto T. Ovitt C.E. Nehrke K. Brugnara C. Alper S.L. Melvin J.E. J. Biol. Chem. 2004; 279: 47681-47687Abstract Full Text Full Text PDF PubMed Scopus (167) Google Scholar). findings the IK1 channel with the KCa3.1 The maxi-K channel is likely encoded by the KCa1.1 gene because from this gene is expressed in parotid acinar cells, and expressed KCa1.1 channels the pharmacological and biophysical as native maxi-K channels (10Nehrke K. Quinn C.C. Begenisich T. Am. J. Physiol. 2003; 284: C535-C546Crossref PubMed Scopus (56) Google Scholar). To confirm the genetic identity of the maxi-K we the parotid acinar cell K+ in wild-type mice and in mice in which the KCa1.1 gene was ablated. The in the and of from the KCa1.1 gene in wild-type and KCa1.1-null as the and maxi-K is from the KCa1.1 gene, parotid acinar cells from KCa1.1-null mice the and voltage-independent IK1 channels. of K+ from a parotid acinar cell from a wild-type mouse are in (11Begenisich T. Nakamoto T. Ovitt C.E. Nehrke K. Brugnara C. Alper S.L. Melvin J.E. J. Biol. Chem. 2004; 279: 47681-47687Abstract Full Text Full Text PDF PubMed Scopus (167) Google the cell of the and maxi-K channels the IK1 channels be this The in show in to a of voltage from a parotid acinar cell with a Ca2+ to a of the cell and maxi-K channels IK1 the in the The of the measured the of the the from maxi-K channels and the strong of IK1 channel the a negative potentials because of IK1 channels and a maxi-K from KCa1.1-null mice and and voltage-independent the of the on and a as the maxi-K of parotid acinar cells in wild-type mice are encoded by the KCa1.1 the of both the KCa1.1 and KCa3.1 the of The of was In other as as cell expected, KCa1.1 gene in the mice was as the a voltage to and was cells from in cells from wild-type of KCa1.1-null and mice revealed an cells from and cells from We also the of IK1 channel in this as the of a voltage negative to allow maxi-K channel mice cells from of IK1 this and the in KCa1.1-null animals was significantly different cells from The in the mice was cells from Parotid in KCa1.1-null we that of IK1 channels or on in fluid secretion in parotid acinar cells (11Begenisich T. Nakamoto T. Ovitt C.E. Nehrke K. Brugnara C. Alper S.L. Melvin J.E. J. Biol. Chem. 2004; 279: 47681-47687Abstract Full Text Full Text PDF PubMed Scopus (167) Google Scholar). IK1 channels are important for fluid secretion, perhaps maxi-K channels However, the in show that fluid secretion with the was by ablation of the KCa1.1 The fluid secretion observed in both KCa1.1-null and animals that K+ channel is necessary for fluid secretion or that either is sufficient to secretion. To between these two we the KCa1.1-null and mice to both K+ channel genes and for parotid gland fluid secretion in the animals. is important to that this a wild-type and result in different fluid secretion this was the as this wild-type a fluid secretion rate A and is for mice with different genetic to in physiological J. T. F. A. H. PubMed Scopus Google Scholar, E.A. B. B. T. Biol. PubMed Scopus Google Scholar, C. T. B. Am. J. Physiol. PubMed Scopus Google Scholar, J. A. H. PubMed Scopus Google Scholar, C. F. U. Eur. J. 2004; PubMed Scopus Google and the secretion rate in these animals to that these animals must be with wild-type animals of the in are the fluid secretion from the animals. is from these results that fluid secretion is significantly both the KCa1.1 and KCa3.1 genes are ablated. of K+ channel is critical for fluid or the other K+ channel must be to fluid secretion. We that the K+ channel KCa3.1 gene a on the ion content of the secreted fluid (11Begenisich T. Nakamoto T. Ovitt C.E. Nehrke K. Brugnara C. Alper S.L. Melvin J.E. J. Biol. Chem. 2004; 279: 47681-47687Abstract Full Text Full Text PDF PubMed Scopus (167) Google Scholar). In the in in the ion content of from the KCa1.1-null are the measured and of the and the osmolality the the the and the from wild-type mice are by and the in from KCa1.1-null animals. The sodium and content and osmolality of in the KCa1.1-null and the potassium content was The but the in the ion content of the secreted from the wild-type for the animals was different from that secreted from the KCa1.1-null wild-type both K+ channel genes the effects as the KCa1.1 but the of the was and, of was also The secreted are in content and osmolality of in a Parotid in and K+ the generally fluid secretion the role of K+ channels in acinar cells is to provide an driving force for Cl– efflux in the of an Cl– which would to the membrane the Cl– is to the parotid acinar cell membrane potentials in wild-type animals and in which either or both K+ channel genes ablated. We measured cell membrane potentials with the both in resting cells and in cells stimulated with of the muscarinic of are in that the resting of parotid acinar cells from wild-type mice was near in the of muscarinic stimulation with The from the cells examined was of a of to near by between and stimulation of salivary gland cells of Ca2+ Melvin J.E. PubMed Scopus Google Scholar, J. Physiol. Scopus Google Scholar, D.I. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, Am. J. Physiol. PubMed Scopus Google resulting in the of Ca2+-activated Cl– and K+ J. Physiol. Scopus Google Scholar, Am. J. Physiol. PubMed Scopus Google Scholar, T. Young J.A. Cook D.I. J. Biol. PubMed Scopus Google Scholar, J. Begenisich T. J. Physiol. PubMed Scopus Google Scholar). The in membrane voltage observed in by the in the of these Cl– and K+ channels. observed in of the cells from wild-type mice that studied and in of the cells from animals. The of the membrane muscarinic stimulation a of among mice with K+ channel genes ablated. of be the the or the we are to the physiological of K+ channel gene is to a membrane voltage for The fluid secretion process a interplay between muscarinic intracellular Ca2+ Ca2+-activated K+ and Cl– channels, and ion by these channels. the membrane that physiological is the value. we the membrane voltage of to parotid acinar cells from wild-type animals and from mice with either or both K+ channel genes ablated. The membrane for wild-type cells that was The membrane voltage for cells that in was significantly different from the for the cells A revealed between the membrane potentials of and cells from K+ animals. In the of cells, likely an in intracellular Ca2+ because we observed a decrease in membrane cells from these cells the of the necessary for and Ca2+ be to be generally intermediate between the with the of K+ and Cl– activated by these Ca2+ be to be to the In as was between and cells, and because the a we cells in the membrane stimulation observed in wild-type mice was The resting membrane of parotid acinar cells from KCa1.1-null mice was with from wild-type in also in the membrane of cells from these The these was significantly different from wild-type We also examined the resting and stimulated membrane potentials in an of which is in The resting of cells from these animals was significantly different from the in cells from wild-type also in cells from these animals the was but significantly in wild-type parotid fluid secretion from these mice is (11Begenisich T. Nakamoto T. Ovitt C.E. Nehrke K. Brugnara C. Alper S.L. Melvin J.E. J. Biol. Chem. 2004; 279: 47681-47687Abstract Full Text Full Text PDF PubMed Scopus (167) Google would that this or on fluid secretion. We also the membrane potentials in mice with both K+ channel genes an of which is in The resting membrane of cells from mice was significantly different from that of cells from wild-type mice that of these K+ channels is responsible for the cell resting This is because channel is likely to be significantly activated these negative the Ca2+ of We of the channels that the cell resting The of channels must be because the cell in the of the KCa1.1 and KCa3.1 channels, is and stimulation of parotid cells from as from of the other membrane as in The in was significantly the in for of the other animals. that either of the K+ channels is sufficient to maintain a negative membrane stimulation but that both K+ channels the of Cl– channels to a in the acinar cells from the animals the driving force for Cl– a efflux of Cl– into the be a and the The content of the acinar secretion that water is for The net result is a a The cells on this fluid to the and but a rate and the membrane potentials in the and of muscarinic stimulation with a of a resting membrane to the or of either or both the Ca2+-activated K+ channels. either K+ channel gene a on the membrane muscarinic with both K+ channels was the stimulated membrane different from the membrane potentials of wild-type and Although the stimulated membrane of cells from mice was significantly the of cells from wild-type and cells, was significantly negative the Cl– ion is the of K+ channels that the of Cl– channels to the the animals these K+ channels, and Cl– channels from the is the The of the K+ channels be to result in a membrane and allow the to a be with the of the of on the membrane of cells from animals is in In the of the to the Cl– The in cells was the Cl– and the in the of The membrane voltage stimulation of cells from wild-type animals was cells from in the of the in the of The membrane of cells in was cells from two that of wild-type cells cells from the of the Ca2+-activated K+ channels membrane stimulation by a of and the of the to the membrane would be to be as large in the animals. of the by the membrane in the animals with the wild-type mice with in Parotid from KCa1.1-null to a many cells and because of the process as in the many cells K+ and Cl– channels in this process (reviewed in Ref. 12Wehner F. Olsen H. Tinel H. Kinne-Saffran E. Kinne R.K. Rev. Physiol. Biochem. Pharmacol. 2003; 148: 1-80Crossref PubMed Scopus (314) Google salivary gland acinar cells J. 1994; PubMed Scopus Google Scholar). We that the KCa3.1 gene in cells but in parotid acinar the maxi-K paxilline in parotid acinar cells (11Begenisich T. Nakamoto T. Ovitt C.E. Nehrke K. Brugnara C. Alper S.L. Melvin J.E. J. Biol. Chem. 2004; 279: 47681-47687Abstract Full Text Full Text PDF PubMed Scopus (167) Google that this Ca2+-activated K+ channel play an important role in this we measured in parotid acinar cells from KCa1.1-null mice and from the wild-type in are the results of the cell volume of acinar cells from wild-type and KCa1.1-null mice in to a in the in was a decrease in the volume of the cells from wild-type the The cells from KCa1.1-null like from wild-type in volume in to the in osmolality wild-type cells, a The rate was from the of these the of the volume This revealed of for cells from wild-type animals and for cells from KCa1.1-null a We found that mice the KCa1.1 gene also lacked the and Ca2+-activated maxi-K channel expressed in parotid gland acinar cells of the parotid acinar cells was substantially inhibited in the KCa1.1-null animals parotid gland fluid secretion was significantly in these mice but in the ion content of the secreted fluid The secreted sodium by in the KCa1.1-null and the secreted potassium was to of that in wild-type animals. with both the KCa1.1 and KCa3.1 genes Ca2+-activated K+ channel and a severely impaired fluid secretion rate animals the alterations in the ion content and osmolality of the secreted fluid as the KCa1.1-null but the The membrane potentials of the acinar cells by muscarinic stimulation the findings with fluid secretion and was in stimulated membrane voltage in and The was between the wild-type and animals. However, the mice a stimulated membrane voltage with the wild-type animals. with that expressed KCa1.1 channels the biophysical and pharmacological as the native maxi-K channels (10Nehrke K. Quinn C.C. Begenisich T. Am. J. Physiol. 2003; 284: C535-C546Crossref PubMed Scopus (56) Google confirm that these channels in parotid acinar cells are encoded by the KCa1.1 This also that the KCa1.1 channel an important role in of these is to that the maxi-K channel role in fluid secretion because was in the fluid secretion rate in the KCa1.1-null The that fluid secretion was also in mice but substantially in animals for a role for these two channels. However, the be because we that of the IK1 channels maxi-K channels J. Begenisich T. J. Physiol. PubMed Scopus Google Scholar). In addition, the of to in fluid secretion from salivary glands for many J.A. E. Pfluegers Arch. Physiol. PubMed Scopus Google Scholar, J.A. S. K. Am. J. Physiol. PubMed Scopus Google Scholar) and used in gene ablation studies K. M. Melvin J.E. J. Biol. Chem. Full Text Full Text PDF PubMed Google a of this of the in the fluid secretion The salivary gland acinar secretion is a fluid in sodium and in but the secreted sodium and potassium J.A. E. Pfluegers Arch. Physiol. PubMed Scopus Google Scholar, J.A. S. K. Am. J. Physiol. PubMed Scopus Google Scholar). the ducts in these glands sodium uptake and potassium secretion a the secreted sodium and potassium the the the is for the sodium secretion resulting in sodium and potassium in the The and content of from KCa1.1-null mice was significantly but the fluid secretion rate was different from that in wild-type animals. the in ion content be by a rate and must in ion in the is on K+ channels in salivary gland but IK1 channels are expressed (10Nehrke K. Quinn C.C. Begenisich T. Am. J. Physiol. 2003; 284: C535-C546Crossref PubMed Scopus (56) Google maxi-K channels are likely in the K+ secretion process in these The of maxi-K channels in the cells would be to a negative membrane and provide a driving force for uptake Ablation of maxi-K channels would be to cell and a driving force for uptake and result in a of secreted as with the KCa1.1-null mice result was the on the muscarinic membrane in the in these animals K+ channel and with of Cl– channels, to maintain a membrane voltage negative the Cl– However, in the of the the membrane to the Cl– this an membrane to the of the K+ can of a to fluid secretion In we that the KCa1.1 gene the Ca2+-activated maxi-K channel in the parotid gland. This channel is necessary for the of these cells, and an important role in sodium secretion in the Although fluid secretion is by ablation of either the KCa1.1 or KCa3.1 gene, both genes severely fluid secretion. Although the of this result is that these two K+ channels roles in fluid secretion, their and in fluid secretion we are to with the in these of fluid secretion and the interplay between the two K+ channels be the of We and for We for with the K+ channel voltage and for this

Перевод пока недоступен