Adenosine triphosphate activates ion permeabilities in biliary epithelial cells

McGill, James M.; Basavappa, Srisaila; Mangel, Allen W.; Shimokura, Gayle H.; Middleton, John; Fitz, John

doi:10.1016/0016-5085(94)90082-5

Cited by 82 publications

(58 citation statements)

References 23 publications

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“…This observation could be explained by the transient nature of the ATP effect on [Ca 2ϩ ] i and by the short-lasting and irregular activation of K ϩ and Cl Ϫ currents. 22,39 Indeed, ATP administered during the course of pH recovery after alkalinization immediately accelerated the rate of HCO 3 Ϫ extrusion in hBDC (Fig. 3).…”

Section: Discussionmentioning

confidence: 84%

“…Stimulation of Ca 2ϩ -activated Cl Ϫ conductance present in biliary epithelial cells, 22 could provide an alternative pathway for stimulation of HCO 3 Ϫ secretion. The supplemental role of non-CFTR Cl Ϫ channels in bile ductular secretion is also supported by the finding that over-expression of Ca 2ϩ -activated Cl Ϫ channels in CFTR (Ϫ/Ϫ) knockout mice could be responsible for lack of cystic fibrosis bile duct lesions.…”

Section: Discussionmentioning

confidence: 99%

“…Purinergic nucleotides are present in bile in concentrations sufficient to activate purinergic receptors. 54 Stimulation of these receptors may promote anion transport both in biliary 18,21,22 and pancreatic 55 duct epithelial cells, at least transiently. 19,20 Interestingly, ATP stimulated HCO 3 Ϫ secretion only in the presence of elevated intracellular cAMP as previously shown.…”

Section: Discussionmentioning

confidence: 99%

“…This current stimulation was transient and current returned towards control values within 1 minute (data not shown). 22,39 Correction of Cl ؊ and HCO 3 ؊ Secretory Defect in CFhBDC by Gentamicin Class I mutations of CFTR, which result in premature stop codons (e.g., G542X) can be corrected with certain aminoglycoside antibiotics. [24][25][26] We pretreated CFhBDC with 200 g/mL gentamicin for 18 hours and measured HCO 3 Ϫ extrusion in the presence of cAMPmix.…”

Section: Ca 2؉ and Camp-dependent CL ؊ Currents In Normal And Cf Cholmentioning

confidence: 99%

“…In addition to cAMP-stimulated Cl Ϫ channels, Ca 2ϩ -activated Cl Ϫ conductances have also been described in both murine 19,20 and human biliary epithelial cells, 21,22 but their relationship to HCO 3 Ϫ secretion and their function in CFTR-deficient cells are unknown. We studied these relationships in both control and CFTR-deficient human bile duct cells.…”

mentioning

confidence: 99%

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Correction of CFTR malfunction and stimulation of Ca2+-activated Cl− channels restore HCO3 − secretion in cystic fibrosis bile ductular cells

et al. 2002

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In view of the occurrence of hepatobiliary disorders in cystic fibrosis (CF) this study addresses the role of the cystic fibrosis transmembrane conductance regulator (CFTR) and of Ca 2؉ -activated Cl ؊ channels in promoting HCO 3 ؊ secretion in bile ductular cells. Human cholangiocytes were isolated from control livers and from 1 patient with CF (⌬F508/G542X mutations). Single channel and whole cell currents were analyzed by patch clamp techniques, and HCO 3 ؊ secretion was determined by fluorometric analysis of the rate of recovery of intracellular pH following alkaline loading. In control cholangiocytes, both cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) catalytic subunit, activated CFTR Cl ؊ channels that exhibited a nonrectifying conductance of 8 pS and appeared in clusters. Activation of Cl ؊ current by cAMP was associated with an increase in the rate of HCO 3 ؊ secretion. The basal rate of HCO 3 ؊ secretion was lower in CF than in control cholangiocytes. In both control and CF cholangiocytes, raising intracellular Ca 2؉ concentrations with ionomycin led to a parallel activation of Cl ؊ current and HCO 3 ؊ secretion. Consistent with reports that premature stop codon mutations (class I; e.g.,

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%