title: Calcium-activated chloride conductance is not increased in pancreatic duct cells of CF mice.
abstract: Calcium-activated anion secretion is elevated in the pancreatic ductal epithelium of transgenic cf/cf mice which lack the cystic fibrosis transmembrane conductance regulator (CFTR). To elucidate whether this effect is due to increased activity of calcium-activated chloride channels, we have studied the relationship between CFTR and calcium-activated chloride currents in pancreatic duct cells isolated from Cambridge cf/cf mice. CFTR chloride currents activated by cAMP were detected in 59% (29/49) of wild-type cells and in 50% (20/40) of heterozygous cells. However, we could not detect any CFTR currents in the homozygous cf/cf cells (0/25). The maximum CFTR current density measured at a membrane potential of 60 mV was 23.5 +/- 2.8 pA/pF (n = 29) in wild-type cells, and about half that value, i.e. 12.4 +/- 1.6 pA/pF (n = 20) in heterozygotes (P = 0.004). Calcium-activated chloride currents were detected in 73% (24/33) of wild-type, 75% (21/28) of heterozygous and in 58% (7/12) of homozygous cf/cf cells. There was no significant difference between the steady-state calcium-activated current densities in the three genotypic groups; the current measured at 60 mV being 527 +/- 162 pA/pF (n = 24) from wild-type, 316 +/- 35 pA/pF (n = 21) from heterozygote and 419 +/- 83 pA/pF (n = 7) from homozygous cells. Our data suggest that lack of CFTR does not enhance the calcium-activated chloride conductance in murine pancreatic duct cells.
authors.affiliation: Department of Physiological Sciences, University Medical School, Newcastle upon Tyne, UK.
authors.forename: J P
authors.initials: JP
authors.lastname: Winpenny
authors.forename: B
authors.initials: B
authors.lastname: Verdon
authors.forename: H L
authors.initials: HL
authors.lastname: McAlroy
authors.forename: W H
authors.initials: WH
authors.lastname: Colledge
authors.forename: R
authors.initials: R
authors.lastname: Ratcliff
authors.forename: M J
authors.initials: MJ
authors.lastname: Evans
authors.forename: M A
authors.initials: MA
authors.lastname: Gray
authors.forename: B E
authors.initials: BE
authors.lastname: Argent
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002712:Chlorides / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004553:Electric Conductivity; D005260:Female; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis; D010183:Pancreatic Ducts / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques
chemical_list: D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D015759:Ionomycin; D000242:Cyclic AMP; D002118:Calcium