Activation of nonselective cation channels by physiological cholecystokinin concentrations in mouse pancreatic acinar cells

Thorn, P. and Petersen, O. H. (1992) Activation of nonselective cation channels by physiological cholecystokinin concentrations in mouse pancreatic acinar cells. Journal of General Physiology, 100 1: 11-25.


Author Thorn, P.
Petersen, O. H.
Title Activation of nonselective cation channels by physiological cholecystokinin concentrations in mouse pancreatic acinar cells
Journal name Journal of General Physiology   Check publisher's open access policy
ISSN 0022-1295
Publication date 1992-07
Sub-type Article (original research)
DOI 10.1085/jgp.100.1.11
Volume 100
Issue 1
Start page 11
End page 25
Total pages 15
Place of publication Baltimore, MD.
Publisher Rockefeller University Press
Language eng
Subject 320300 Medical Biochemistry and Clinical Chemistry
Abstract The activation of the nonselective cation channels in mouse pancreatic acinar cells has been assessed at low agonist concentrations using patch-clamp whole cell, cell-attached patch, and isolated inside-out patch recordings. Application of acetylcholine (ACh) (25-1,000 nM) and cholecystokinin (CCK) (2-10 pM) evoked oscillatory responses in both cation and chloride currents measured in whole cell experiments. In cell-attached patch experiments we demonstrate CCK and ACh evoked opening of single 25-pS cation channels in the basolateral membrane. Therefore, at least a component of the whole cell cation current is due to activation of cation channels in the basolateral acinar cell membrane. To further investigate the reported sensitivity of the cation channel to intracellular ATP and calcium we used excised inside-out patches. Micromolar Ca2+ concentrations were required for significant channel activation. Application of ATP and ADP to the intracellular surface of the patch blocked channel opening at concentrations between 0.2 and 4 mM. The nonmetabolizable ATP analogue, 5'- adenylylimidodiphosphate (AMP-PNP, 0.2-2 mM), also effectively blocked channel opening. The subsequent removal of ATP caused a transient increase in channel activity not seen with the removal of ADP or AMP- PNP. Patches isolated into solutions containing 2 mM ATP showed channel activation at micromolar Ca2+ concentrations. Our results show that ATP has two separate effects. The continuous presence of the nucleotide is required for operation of the cation channels and this action seems to depend on ATP hydrolysis. ATP can also close the channel and this effect can be demonstrated in excised inside-out patches when ATP is added to the bath after a period of exposure to an ATP-free solution. This action does not require ATP hydrolysis. Under physiological conditions hormonal stimulation can open the nonselective cation channels and this can be explained by the rise in the intracellular free Ca2+ concentration.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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