MISC

2004年7月

Gramicidin-perforated patch recording revealed the oscillatory nature of secretory Cl- movements in salivary acinar cells

Journal of General Physiology
  • Makoto Sugita
  • ,
  • Chikara Hirono
  • ,
  • Yoshiki Shiba

124
1
開始ページ
59
終了ページ
69
記述言語
英語
掲載種別
DOI
10.1085/jgp.200308948

Elevations of cytoplasmic free calcium concentrations ([Ca 2-]i) evoked by cholinergic agonists stimulate isotonic fluid secretion in salivary acinar cells. This process is driven by the apical exit of Cl- through Ca2+-activated Cl- channels, while Cl- enters the cytoplasm against its electrochemical gradient via a loop diuretic-sensitive Na+-K+-2Cl - cotransporter (NKCC) and/or parallel operations of Cl --HCO3- and Na+-H+ exchangers, located in the basolateral membrane. To characterize the contributions of those activities to net Cl- secretion, we analyzed carbachol (CCh)-activated Cl- currents in submandibular acinar cells using the "gramicidin-perforated patch recording configuration." Since the linear polypeptide antibiotic gramicidin creates monovalent cation-selective pores, CCh-activated Cl- currents in the gramicidin-perforated patch recording were carried by Cl- efflux via Cl- channels, dependent upon Cl- entry through Cl - transporters expressed in the acinar cells. CCh-evoked oscillatory Cl- currents were associated with oscillations of membrane potential. Bumetanide, a loop diuretic, decreased the CCh-activated Cl- currents and hyperpolarized the membrane potential. In contrast, neither methazolamide, a carbonic anhydrase inhibitor, nor elimination of external HCO3- had significant effects, suggesting that the cotransporter rather than parallel operations of Cl--HCO 3- and Na+-H+ exchangers is the primary Cl- uptake pathway. Pharmacological manipulation of the activities of the Ca2+-activated Cl- channel and the NKCC revealed that the NKCC plays a substantial role in determining the amplitude of oscillatory Cl- currents, while adjusting to the rate imposed by the Ca2+-activated Cl- channel, in the gramicidin-perforated patch configuration. By concerting with and being controlled by the cation steps, the oscillatory form of secretory Cl- movements may effectively provide a driving force for fluid secretion in intact acinar cells.

リンク情報
DOI
https://doi.org/10.1085/jgp.200308948
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/15226364

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