Calcium-activated chloride currents and non-selective cation channels in a novel cystic fibrosis-derived human pancreatic duct cell line.
The modulation of ion fluxes across the plasma membrane of epithelial cells is central for fluid secretion and absorption. Their disruption can lead to pathological states. An example is cystic fibrosis (CF), a disease characterized by abnormal functioning of the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-modulated chloride channel. Here we report the characterization of calcium-activated, DIDS sensitive chloride current and non-selective calcium-activated cation channels in a novel human pancreatic duct cell line (YHV-1) derived from a non-delta F508 mutation CF patient bearing a severe phenotype. Southern blot analysis of the CFTR gene indicates a distinct electrophoretic pattern for the region spanned by exons 15-24, a result presumably related to a mutation which has yet to be identified. In contrast to large calcium-activated chloride currents there were no cAMP-dependent CFTR-type chloride currents. Non-selective cation channels were blocked by intracellular ATP and activated by intracellular calcium and cAMP. We propose the cell line YHV-1 as a suitable model for studying pancreatic ion and fluid secretion alterations in CF.
Eguiguren
A L
AL
Departamento de Medicina Experimental, Facultad de Medicina, Universidad de Chile, Santiago.
Ríos
J
J
Riveros
N
N
Sepúlveda
F V
FV
Stutzin
A
A
D015139:Blotting, Southern; D002118:Calcium / Q000378:metabolism*; D002412:Cations; D002460:Cell Line; D002675:Child, Preschool; D018118:Chloride Channels / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D018076:DNA, Complementary; D005260:Female; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D010183:Pancreatic Ducts / Q000166:cytology / Q000378:metabolism* / Q000502:physiology
C505032:CFTR protein, human; D002412:Cations; D018118:Chloride Channels; D018076:DNA, Complementary; D007473:Ion Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP; D002118:Calcium