|
|
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The Journal of General Physiology, Vol 100, 11-25, Copyright © 1992 by The Rockefeller University Press
ARTICLES |
P Thorn and OH Petersen
Medical Research Council Secretory Control Research Group, University of Liverpool, United Kingdom.
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.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Chung and S. D. Moore Cholecystokinin Excites Interneurons in Rat Basolateral Amygdala J Neurophysiol, July 1, 2009; 102(1): 272 - 284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Zhang, Z. Zhao, R. Margolskee, and E. Liman The Transduction Channel TRPM5 Is Gated by Intracellular Calcium in Taste Cells J. Neurosci., May 23, 2007; 27(21): 5777 - 5786. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Turvey, K. E. Fogarty, and P. Thorn Inositol (1,4,5)-trisphosphate receptor links to filamentous actin are important for generating local Ca2+ signals in pancreatic acinar cells J. Cell Sci., March 1, 2005; 118(5): 971 - 980. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Pickett, P. Thorn, and J. M. Edwardson The Plasma Membrane Q-SNARE Syntaxin 2 Enters the Zymogen Granule Membrane during Exocytosis in the Pancreatic Acinar Cell J. Biol. Chem., January 14, 2005; 280(2): 1506 - 1511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yamasaki, R. Masgrau, A. J. Morgan, G. C. Churchill, S. Patel, S. J. H. Ashcroft, and A. Galione Organelle Selection Determines Agonist-specific Ca2+ Signals in Pancreatic Acinar and {beta} Cells J. Biol. Chem., February 20, 2004; 279(8): 7234 - 7240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R Liman Regulation by voltage and adenine nucleotides of a Ca2+-activated cation channel from hamster vomeronasal sensory neurons J. Physiol., May 1, 2003; 548(3): 777 - 787. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. G. Hurwitz, V. Y. Hu, and A. S. Segal A mechanogated nonselective cation channel in proximal tubule that is ATP sensitive Am J Physiol Renal Physiol, July 1, 2002; 283(1): F93 - F104. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. K. Park, R. B. Lomax, A. V. Tepikin, and O. H. Petersen Local uncaging of caged Ca2+ reveals distribution of Ca2+-activated Cl- channels in pancreatic acinar cells PNAS, September 4, 2001; (2001) 181353798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Chen and J. M. Simard Cell Swelling and a Nonselective Cation Channel Regulated by Internal Ca2+ and ATP in Native Reactive Astrocytes from Adult Rat Brain J. Neurosci., September 1, 2001; 21(17): 6512 - 6521. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Inoue and Y. Ito Intracellular ATP slows time-dependent decline of muscarinic cation current in guinea pig ileal smooth muscle Am J Physiol Cell Physiol, November 1, 2000; 279(5): C1307 - C1318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E Fogarty, J. F Kidd, D. A Tuft, and P. Thorn Mechanisms underlying InsP3-evoked global Ca2+ signals in mouse pancreatic acinar cells J. Physiol., August 1, 2000; 526(3): 515 - 526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J F Kidd, K E Fogarty, R A Tuft, and P Thorn The role of Ca2+ feedback in shaping InsP3-evoked Ca2+ signals in mouse pancreatic acinar cells J. Physiol., October 1, 1999; 520(1): 187 - 201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C Camello, J A Pariente, G M Salido, and P J Camello Sequential activation of different Ca2+ entry pathways upon cholinergic stimulation in mouse pancreatic acinar cells J. Physiol., April 15, 1999; 516(2): 399 - 408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Giovannucci, G. E. Groblewski, J. Sneyd, and D. I. Yule Targeted Phosphorylation of Inositol 1,4,5-Trisphosphate Receptors Selectively Inhibits Localized Ca2+ Release and Shapes Oscillatory Ca2+ Signals J. Biol. Chem., October 20, 2000; 275(43): 33704 - 33711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Fogarty, J. F. Kidd, A. Turner, J. N. Skepper, J. Carmichael, and P. Thorn Microtubules Regulate Local Ca2+ Spiking in Secretory Epithelial Cells J. Biol. Chem., July 14, 2000; 275(29): 22487 - 22494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Park, R. B. Lomax, A. V. Tepikin, and O. H. Petersen Local uncaging of caged Ca2+ reveals distribution of Ca2+-activated Cl- channels in pancreatic acinar cells PNAS, September 11, 2001; 98(19): 10948 - 10953. [Abstract] [Full Text] [PDF]
|
|
|
|
