Modulation of Cl- secretion by benzimidazolones. II. Coordinate regulation of apical GCl and basolateral GK

1996 ◽  
Vol 271 (5) ◽  
pp. L785-L795 ◽  
Author(s):  
D. C. Devor ◽  
A. K. Singh ◽  
R. J. Bridges ◽  
R. A. Frizzell
Keyword(s):  
Cystic Fibrosis ◽  
Basolateral Membrane ◽  
Primary Cultures ◽  
Secretory Response ◽  
K Channel ◽  
T84 Cells ◽  
Coordinate Regulation ◽  
Cl Secretion ◽  
Cl Channels ◽  
Subsequent Addition

We previously demonstrated that the novel benzimidazolone, 1-ethyl-2-benzimidazolinone (1-EBIO), stimulates a sustained Cl- secretory response across T84 monolayers by opening a Ca(2+)-dependent basolateral K+ channel. In the present work, we evaluated the effects on Cl-secretion of other benzimidazolones, NS-004 and NS-1619, which have been shown to open cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels. In contrast to 1-EBIO, neither NS-004 nor NS-1619 stimulated a significant Cl- secretory current (Isc). Neither NS-004 nor NS-1619 increased Isc subsequent to forskolin stimulation. However, when added after 1-EBIO, NS-004 and NS-1619 stimulated large sustained increases in Isc. In addition, NS-004 and NS-1619 potentiated the effects of carbachol. We used nystatin to permeabilize the apical or basolateral membrane to determine the effects of NS-004 and 1-EBIO on the basolateral K+ (IK) and apical Cl- (ICl) currents. Both NS-004 and 1-EBIO increased ICl, and the stimulated currents were inhibited by glibenclamide. In contrast, NS-004 failed to significantly affect IK, but subsequent addition of 1-EBIO induced a large increase in IK. The effects of 1-EBIO, NS-004, and NS-1619 on the Ca(2+)-dependent K+ channel (KCa) in T84 cells was determined in excised inside-out patches. Neither NS-004 nor NS-1619 affected K+ channel activity, whereas the subsequent addition of 1-EBIO produced a marked channel activation. Results similar to those observed in T84 monolayers were obtained from murine airway cell primary cultures: NS-004 or NS-1619 had no effect on Isc, whereas 1-EBIO stimulated a sustained Cl- secretory response. The results demonstrate that activation of CFTR alone is insufficient to evoke transepithelial Cl- secretion. Activation of the basolateral membrane K+ channel is a necessary component of the secretory response. Thus the basolateral membrane KCa may be a novel pharmacological target in cystic fibrosis therapy.

Modulation of Cl- secretion by benzimidazolones. I. Direct activation of a Ca(2+)-dependent K+ channel

1996 ◽  
Vol 271 (5) ◽  
pp. L775-L784 ◽  
Author(s):  
D. C. Devor ◽  
A. K. Singh ◽  
R. A. Frizzell ◽  
R. J. Bridges
Keyword(s):  
Short Circuit ◽  
Basolateral Membrane ◽  
Primary Cultures ◽  
Short Circuit Current ◽  
Secretory Response ◽  
K Channel ◽  
T84 Cells ◽  
K Channels ◽  
Cl Secretion ◽  
Direct Activation

We evaluated the effects of the novel benzimidazolone, 1-ethyl-2-benzimidazolinone (1-EBIO), on Cl- secretion across T84 monolayers. 1-EBIO stimulated a sustained Cl- secretory response at a half-maximal effective concentration of 490 microM. Charybdotoxin (CTX) inhibited the 1-EBIO-induced short-circuit current (Isc) with an inhibitory constant (Ki) of 3.6 nM, whereas 293B, an inhibitor of adenosine 3',5'-cyclic monophosphate-activated K+ channels, had no effect on the current induced by 1-EBIO. In contrast, CTX failed to inhibit the 293B-sensitive forskolin-induced Isc. The above results suggested that 1-EBIO may be activating the basolateral membrane Ca(2+)-dependent K+ channel (KCa) in these cells. This was further confirmed using nystatin to permeabilize the apical membrane in the presence of a mucosa-to-serosa K+ gradient and determining the effects of 1-EBIO on the basolateral K+ current (IK). Under these conditions, 1-EBIO induced a large increase in IK that was blocked by CTX. In membrane vesicles prepared from T84 cells, 1-EBIO stimulated 86Rb+ uptake in a CTX-sensitive manner; the Ki for inhibition by CTX was 3.5 nM. Similar to our intact monolayer studies, this 86Rb+ uptake was not blocked by 293B. The effects of 1-EBIO on the KCa in T84 cells was determined in excised inside-out patches. 1-EBIO (100 microM) increased the product of the number of channels and the open channel probability from 0.09 +/- 0.03 to 1.17 +/- 0.27 (n = 8); this effect on KCa activity required a minimal level of free Ca2+. Similar to its effect on T84 cells, 1-EBIO stimulated a sustained Cl- secretory current in rat colonic epithelium, which was partially blocked by CTX. Finally, 1-EBIO stimulated a sustained Cl- secretory response in primary cultures of murine tracheal epithelium. We conclude that the benzimidazolone, 1-EBIO, stimulates Cl- secretion in secretory epithelia via the direct activation of a Kca. 1-EBIO is the first pharmacological opener of this important class of epithelial K+ channels to be identified.

Psoralens: novel modulators of Cl- secretion

1997 ◽  
Vol 272 (3) ◽  
pp. C976-C988 ◽  
Author(s):  
D. C. Devor ◽  
A. K. Singh ◽  
R. J. Bridges ◽  
R. A. Frizzell
Keyword(s):  
Short Circuit ◽  
Basolateral Membrane ◽  
Primary Cultures ◽  
Receptor Activation ◽  
Sustained Response ◽  
Rat Colon ◽  
Cl Secretion ◽  
Cl Channel ◽  
Cl Channels ◽  
Cl Conductance

We evaluated effects of psoralens on Cl- secretion (short-circuit current, I(sc)) across T84 monolayers. Methoxsalen failed to increase I(sc). Several observations suggest that psoralens open cystic fibrosis transmembrane conductance regulator Cl- channels. 1) After activation of the Ca2+-dependent basolateral membrane K+ channel (K(Ca)) by 1-ethyl-2-benzimidazolinone or thapsigargin, methoxsalen (10 microM) further increased I(sc). 2) When added before carbachol (CCh), methoxsalen potentiated the I(sc) response to CCh, as predicted, if it increased apical Cl- conductance. 3) After establishment of a mucosal-to-serosal Cl- gradient and permeabilization of basolateral membrane with nystatin, psoralens increased Cl- current, which was inhibited by glibenclamide. In contrast, neither TS-TM calix[4]arene nor Cd2+, inhibitors of outwardly rectifying Cl- channels and the ClC-2 Cl-channel, respectively, inhibited psoralen-induced Cl- current. In contrast to their effects on Cl- conductance, psoralens failed to significantly affect basolateral membrane K+ conductance; subsequent addition of 1-ethyl-2-benzimidazolinone induced a large increase in K+ conductance. Also, in excised patches, methoxsalen failed to activate K(Ca). In addition to potentiating the peak response to CCh, psoralens induced a secondary, sustained response. Indeed, when added up to 60 min after return of CCh-induced I(sc) to baseline, psoralens induced a sustained I(sc). This sustained response was inhibited by atropine, demonstrating the requirement for continuous muscarinic receptor activation by CCh. This sustained response was inhibited also by verapamil, removal of bath Ca2+, and charybdotoxin. These results suggest that return of I(sc) to baseline after CCh stimulation is not due to downregulation of Ca2+ influx or K(Ca). Finally, we obtained similar results with psoralens in rat colon and primary cultures of murine tracheal epithelium. On the basis of these observations, we conclude that psoralens represent a novel class of Cl- channel openers that can be used to probe mechanisms underlying Ca2+-mediated Cl- secretion.

Potassium dependence of Na-Cl cotransport in dog tracheal epithelium

1991 ◽  
Vol 261 (4) ◽  
pp. L290-L295 ◽  
Author(s):  
P. Fong ◽  
A. C. Chao ◽  
J. H. Widdicombe
Keyword(s):  
Short Circuit ◽  
Basolateral Membrane ◽  
Primary Cultures ◽  
Short Circuit Current ◽  
Tracheal Epithelium ◽  
K Channel ◽  
Cl Secretion ◽  
Nacl Cotransport ◽  
Entry Mechanism

In confluent primary cultures of dog tracheal epithelium, we tested whether Cl entry across the basolateral membrane is by cotransport with K. Two approaches were taken. First, we measured the inhibition of short-circuit current (Isc) by the K channel inhibitor, Ba2+. Consistent with Na-K-2Cl cotransport, maximal doses of Ba2+ inhibited five-sixths of Isc in tissues previously stimulated to secrete Cl; only two-thirds of Isc should be sensitive to Ba2+ if NaCl cotransport is the entry mechanism. Second, we measured basolateral 86Rb uptake and demonstrated inhibition by bumetanide, an inhibitor of Na-K-2Cl cotransport in other tissues. The degree of inhibition by bumetanide was consistent with the levels of Cl secretion measured as Isc. Uptake of 86Rb was also reduced by removal of Na or Cl, and under these conditions Rb uptake was not further inhibited by bumetanide. These results suggest that the process responsible for Cl entry across the basolateral membrane of tracheal epithelium during Cl secretion is Na-K-2Cl rather than Na-Cl cotransport.

Apical and basolateral ATP stimulates tracheal epithelial chloride secretion via multiple purinergic receptors

1996 ◽  
Vol 270 (6) ◽  
pp. C1611-C1623 ◽  
Author(s):  
T. H. Hwang ◽  
E. M. Schwiebert ◽  
W. B. Guggino
Keyword(s):  
Cystic Fibrosis ◽  
Purinergic Receptors ◽  
Basolateral Membrane ◽  
Receptor Subtypes ◽  
Cl Secretion ◽  
Cl Channel ◽  
Basolateral Side ◽  
Channel Blocking ◽  
Cl Channels ◽  
Tracheal Epithelial

Stimulation of Cl- secretion across the airway epithelium by ATP or UTP as agonists has therapeutic implications for cystic fibrosis. Our results demonstrate that ATP stimulates Cl- secretion in rat tracheal epithelial cell monolayers in primary culture from the apical or basolateral side of the monolayer. Multiple types of ATP-sensitive Cl- conductances in intact monolayers were elucidated through inhibition by Cl- channel-blocking drugs. Multiple Cl- conductances stimulated by ATP and adenosine 3',5'-cyclic monophosphate (cAMP) (tested for comparison) were also deciphered more specifically by nystatin permeabilization of the basolateral membrane, subsequent imposition of symmetrical Cl-, I-, or Br- solutions to test halide permselectivity, inhibition by Cl- channel-blocking drugs, and construction of current-voltage plots to study time and voltage dependence of the currents. Apical ATP stimulates Cl- secretion through P2U (or P2Y2) purinergic receptors via both intracellular Ca2+ (Ca(2+)i)-dependent and Cai(2+)-independent signaling pathways by opening outwardly rectifying Cl- channels (ORCCs), cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels, and Cai(2+)-dependent Cl- channels. Basolateral ATP stimulates Cl- secretion via a combination of receptor subtypes (P2T and P2U) or a novel type of receptor (P2Y3), independent of Cai2+ or cAMP signaling by opening only CFTR channels. cAMP also stimulated multiple types of Cl- conductances, consistent with simultaneous activation of CFTR and ORCCs. Together, these results suggest that ATP as an agonist stimulates Cl- secretion via multiple purinergic receptors and multiple signal transduction pathways activated in different membrane domains of tracheal epithelia.

Activation of CFTR Cl- conductance in polarized T84 cells by luminal extracellular ATP

1995 ◽  
Vol 268 (2) ◽  
pp. C425-C433 ◽  
Author(s):  
M. J. Stutts ◽  
E. R. Lazarowski ◽  
A. M. Paradiso ◽  
R. C. Boucher
Keyword(s):  
Adenosine Receptor ◽  
Apical Membrane ◽  
Short Circuit ◽  
Basolateral Membrane ◽  
Apical Cell ◽  
Extracellular Atp ◽  
T84 Cells ◽  
Apical Cell Membrane ◽  
Cl Secretion ◽  
Cl Conductance

Luminal extracellular ATP evoked a bumetanide-sensitive short-circuit current in cultured T84 cell epithelia (90.2 +/- 18.2 microA/cm2 at 100 microM ATP, apparent 50% effective concentration, 11.5 microM). ATP appeared to increase the Cl- conductance of the apical membrane but not the driving force for Cl- secretion determined by basolateral membrane K+ conductance. Specifically, the magnitude of Cl- secretion stimulated by ATP was independent of basal current, and forskolin pretreatment abolished subsequent stimulation of Cl- secretion by ATP. Whereas ATP stimulated modest production of adenosine 3',5'-cyclic monophosphate (cAMP) by T84 cells, ATP caused smaller increases in intracellular Ca2+ and inositol phosphate activities than the Ca(2+)-signaling Cl- secretagogue carbachol. An inhibitor of 5'-nucleotidase, alpha,beta-methyleneadenosine 5'-diphosphate, blocked most of the response to luminal ATP. The adenosine receptor antagonist 8-(p-sulfophenyl)theophylline blocked both the luminal ATP-dependent generation of cAMP and Cl- secretion when administered to the luminal but not submucosal bath. These results demonstrate that the Cl- secretion stimulated by luminal ATP is mediated by a A2-adenosine receptor located on the apical cell membrane. Thus metabolism of extracellular ATP to adenosine regulates the activity of cystic fibrosis transmembrane conductor regulator (CFTR) in the apical membrane of polarized T84 cells.

scholarly journals Effect of ATP-sensitive K+ channel regulators on cystic fibrosis transmembrane conductance regulator chloride currents.

1992 ◽  
Vol 100 (4) ◽  
pp. 573-591 ◽  
Author(s):  
D N Sheppard ◽  
M J Welsh
Keyword(s):  
Cystic Fibrosis ◽  
Voltage Dependence ◽  
K Channel ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
K Channels ◽  
Intracellular Atp ◽  
Cl Channel ◽  
Cl Channels ◽  
Cystic Fibrosis Transmembrane

The cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl- channel that is regulated by cAMP-dependent phosphorylation and by intracellular ATP. Intracellular ATP also regulates a class of K+ channels that have a distinct pharmacology: they are inhibited by sulfonylureas and activated by a novel class of drugs called K+ channel openers. In search of modulators of CFTR Cl- channels, we examined the effect of sulfonylureas and K+ channel openers on CFTR Cl- currents in cells expressing recombinant CFTR. The sulfonylureas, tolbutamide and glibenclamide, inhibited whole-cell CFTR Cl- currents at half-maximal concentrations of approximately 150 and 20 microM, respectively. Inhibition by both agents showed little voltage dependence and developed slowly; > 90% inhibition occurred 3 min after adding 1 mM tolbutamide or 100 microM glibenclamide. The effect of tolbutamide was reversible, while that of glibenclamide was not. In contrast to their activating effect on K+ channels, the K+ channel openers, diazoxide, BRL 38227, and minoxidil sulfate inhibited CFTR Cl- currents. Half-maximal inhibition was observed at approximately 250 microM diazoxide, 50 microM BRL 38227, and 40 microM minoxidil sulfate. The rank order of potency for inhibition of CFTR Cl- currents was: glibenclamide < BRL 38227 approximately equal to minoxidil sulfate > tolbutamide > diazoxide. Site-directed mutations of CFTR in the first membrane-spanning domain and second nucleotide-binding domain did not affect glibenclamide inhibition of CFTR Cl- currents. However, when part of the R domain was deleted, glibenclamide inhibition showed significant voltage dependence. These agents, especially glibenclamide, which was the most potent, may be of value in identifying CFTR Cl- channels. They or related analogues might also prove to be of value in treating diseases such as diarrhea, which may involve increased activity of the CFTR Cl- channel.

scholarly journals Zinc inhibits cAMP-stimulated Cl secretion via basolateral K-channel blockade in rat ileum

2005 ◽  
Vol 288 (5) ◽  
pp. G956-G963 ◽  
Author(s):  
Kazi Mirajul Hoque ◽  
Vazhaikkurichi M. Rajendran ◽  
Henry J. Binder
Keyword(s):  
Short Circuit ◽  
Basolateral Membrane ◽  
Short Circuit Current ◽  
K Channel ◽  
Isolated Cells ◽  
Rat Ileum ◽  
Anion Secretion ◽  
Cl Secretion ◽  
Ion Absorption ◽  
Isotonic Buffer

Zn, an essential micronutrient and second most abundant trace element in cell and tissues, reduces stool output when administered to children with acute diarrhea. The mechanism by which Zn improves diarrhea is not known but could result from stimulating Na absorption and/or inhibiting anion secretion. The aim of this study was to investigate the direct effect of Zn on intestinal epithelial ion absorption and secretion. Rat ileum was partially stripped of serosal and muscle layers, and the mucosa was mounted in lucite chambers. Potential difference and short-circuit current were measured by conventional current-voltage clamp method.86Rb efflux and uptake were assessed for serosal K channel and Na-K-2Cl cotransport activity, respectively. Efflux experiments were performed in isolated cells preloaded with86Rb in the presence of ouabain and bumetanide, whereas uptake experiments were performed in low-Cl isotonic buffer containing Ba and ouabain. Neither mucosal nor serosal Zn affected glucose-stimulated Na absorption. In contrast, forskolin-induced Cl secretion was markedly reduced by serosal but not mucosal addition of Zn. Zn also substantially reversed the increase in Cl secretion induced by 8-bromoadenosine 3′,5′-cyclic monophosphate (8-BrcAMP) with half-maximal inhibitory concentration of 0.43 mM. In contrast, serosal Zn did not alter Cl secretion stimulated by carbachol, a Ca-dependent agonist. Zn inhibited 8-BrcAMP-stimulated86Rb efflux but not carbachol-stimulated86Rb efflux. Zn had no effect on bumetanide-sensitive86Rb uptake, Na-K-ATPase, or CFTR. We conclude from these studies that Zn inhibits cAMP-induced Cl secretion by blocking basolateral membrane K channels.

Human colonic subepithelial myofibroblasts modulate transepithelial resistance and secretory response

1999 ◽  
Vol 277 (2) ◽  
pp. C271-C279 ◽  
Author(s):  
J. Beltinger ◽  
B. C. McKaig ◽  
S. Makh ◽  
W. A. Stack ◽  
C. J. Hawkey ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Barrier Function ◽  
Transforming Growth Factor ◽  
Short Circuit ◽  
Primary Cultures ◽  
Short Circuit Current ◽  
Transforming Growth Factor Β ◽  
Secretory Response ◽  
Transepithelial Resistance ◽  
T84 Cells

The epithelium of the gastrointestinal tract transports ions and water but excludes luminal microorganisms and toxic molecules. The factors regulating these important functions are not fully understood. Intestinal myofibroblasts lie subjacent to the basement membrane, at the basal surface of epithelial cells. We recently showed that primary cultures of adult human colonic subepithelial myofibroblasts express cyclooxygenase (COX)-1 and COX-2 enzymes and release bioactive transforming growth factor-β (TGF-β). In this study we have investigated the role of normal human colonic subepithelial myofibroblasts in the regulation of transepithelial resistance and secretory response in HCA-7 and T84 colonic epithelial cell lines. Cocultures of epithelial cells-myofibroblasts and medium conditioned by myofibroblasts enhanced transepithelial resistance and delayed mannitol flux. A panspecific antibody to TGF-β (but not piroxicam) antagonized this effect. In HCA-7 cells, myofibroblasts downregulated secretagogue-induced change in short-circuit current, and this effect was reversed by pretreatment of myofibroblasts with piroxicam. In contrast to HCA-7 cells, myofibroblasts upregulated the agonist-induced secretory response in T84 cells. This study shows that intestinal subepithelial myofibroblasts enhance barrier function and modulate electrogenic chloride secretion in epithelial cells. The enhancement of barrier function was mediated by TGF-β. In contrast, the modulation of agonist-induced change in short-circuit current was mediated by cyclooxygenase products. These findings suggest that colonic myofibroblasts regulate important functions of epithelial cells via distinct secretory products.

Inhibition of cAMP- and Ca-dependent Cl- secretion by phorbol esters: inhibition of basolateral K+ channels

1993 ◽  
Vol 264 (1) ◽  
pp. C161-C168 ◽  
Author(s):  
W. W. Reenstra
Keyword(s):  
Phorbol Esters ◽  
Short Circuit ◽  
Short Circuit Current ◽  
T84 Cells ◽  
K Channels ◽  
Cl Secretion ◽  
Cyclic Monophosphate ◽  
Regulator Protein ◽  
Cl Channels ◽  
Cl Conductance

Pretreating confluent T84 cells with the phorbol ester phorbol 12-myristate 13-acetate (PMA) inhibits adenosine 3',5'-cyclic monophosphate (cAMP)- and carbachol-induced Cl secretion. Both a sustained short-circuit current (Isc), seen after the addition of 50 microM 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate (CPT-cAMP) and 100 microM 3-isobutyl-1-methylxanthine (IBMX), and a transient current, seen after the subsequent addition of 100 microM carbachol, are inhibited by 80% following pretreatment with 100 nM PMA for 2 h. Pretreatment with PMA has no effect on the level of cystic fibrosis transmembrane conductance regulator protein or apical cAMP-dependent Cl conductance. Carbachol does not induce an increase in apical Cl conductance. Basolateral K conductance was measured in monolayers treated with apical nystatin and exposed to a K gradient. Agonist-independent K conductance is 10-fold greater in Cl media than in gluconate media. Pretreatment with PMA inhibits agonist-independent K conductance by 57% in Cl media but stimulates K conductance by 1.9-fold in gluconate media. The addition of carbachol induces a transient increase in basolateral K conductance, and pretreatment with PMA inhibits the agonist-dependent K conductance by 66% in Cl media and by 92% in gluconate media. In Cl media, serosal barium, at 3 mM, inhibits agonist-independent K conductance but has no significant effect on the carbachol-induced conductance. In nonpermeabilized monolayers, serosal barium inhibits the cAMP-dependent Isc by 56% but has no effect on the carbachol-induced Isc. These results demonstrate that the primary effect of PMA on Cl secretion is not inhibition of apical Cl channels but inhibition of basolateral K channels.(ABSTRACT TRUNCATED AT 250 WORDS)

cAMP- but not Ca(2+)-regulated Cl- conductance is lacking in cystic fibrosis mice epididymides and seminal vesicles

1996 ◽  
Vol 271 (1) ◽  
pp. C188-C193 ◽  
Author(s):  
A. Y. Leung ◽  
P. Y. Wong ◽  
J. R. Yankaskas ◽  
R. C. Boucher
Keyword(s):  
Cystic Fibrosis ◽  
Secretory Pathway ◽  
Short Circuit ◽  
Primary Cultures ◽  
Seminal Vesicles ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Cl Secretion ◽  
Induced Changes ◽  
Cystic Fibrosis Transmembrane

Cystic fibrosis (CF) reflects the loss of adenosine 3',5'-cyclic monophosphate (cAMP)-regulated Cl- secretion consequent to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In humans, but not mice, with CF, the disease is associated with male infertility. The present study investigated the relative magnitudes of the cAMP pathways and an alternative Ca(2+)-regulated Cl- secretory pathway in primary cultures of the epididymides and the seminal vesicles of normal and CF mice. The basal equivalent short-circuit currents (Ieq) of cultures derived from the epididymides and the seminal vesicles from the CF mice were lower (6.0 +/- 0.6 and 4.0 +/- 1.0 muA/cm2, respectively) than those from normal mice (11.1 +/- 1.0 and 6.6 +/- 0.6 muA/cm2, respectively). Forskolin induced significant Ieq responses in both the epididymis (8.0 +/- 0.7 muA/cm2) and seminal vesicles (4.0 +/- 0.5 muA/cm2) from normal mice, whereas forskolin-induced changes in Ieq in CF mouse epididymis and seminal vesicles were absent, consistent with defective cAMP-CFTR-mediated Cl- secretion in CF mice. Ieq responses to agonists (ionomycin, ATP) that raise intracellular Ca2+ (Ca2+i) were larger than forskolin responses in normal animals (6.6 +/- 0.9 and 13.4 +/- 1.8 muA/cm2, respectively) and were preserved in CF (6.5 +/- 0.9 and 17.1 +/- 1.0 muA/cm2, respectively). We speculate that the fertility of male CF mice is maintained by persistent expression of the predominant alternative Ca(2+)-mediated Cl- transport system in the epididymides and seminal vesicles.

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