2-Aminoethoxydiphenyl Borate Modulates Kinetics of Intracellular Ca2+ Signals Mediated by Inositol 1,4,5-Trisphosphate-Sensitive Ca2+ Stores in Single Pancreatic Acinar Cells of Mouse (original) (raw)
Research ArticleArticle
, Noritaka Kamimura, Teruko Takeo, Sechiko Suga, Makoto Wakui, Takayuki Maruyama and Katsuhiko Mikoshiba
Molecular Pharmacology December 2000, 58 (6) 1368-1374; DOI: https://doi.org/10.1124/mol.58.6.1368
Abstract
Regulation of the kinetics of intracellular Ca2+ signals with a novel, membrane-penetrable, inositol 1,4,5-trisphosphate (InsP3) receptor/Ca2+ channel modulator, 2-amino-ethoxydiphenyl borate (2APB), has been investigated using patch-clamp, whole-cell recording to monitor Ca2+-activated Cl− currents in single isolated pancreatic acinar cells. 2APB itself fails to evoke a detectable current response but it dramatically changes the kinetics of agonist-induced Ca2+release from pulsatile spikes to long-lasting, huge Ca2+waves, suggesting that 2APB coordinates local Ca2+ release to generate global Ca2+ signals. The regulation by 2APB can be elicited by internal perfusion of InsP3 in a concentration-dependent manner, indicating that this regulation is not mediated through membrane receptors or G protein signal transduction. The InsP3 receptor blocker heparin, but not the ryanodine-sensitive receptor blockers ruthenium red or ryanodine, abolishes 2APB-mediated regulation of Ca2+ release. This results also suggest that 2APB effects are mediated through InsP3 receptors. 2APB substantially modifies single inward Cl− current pulse evoked by the photolytic release of caged InsP3 but not by caged Ca2+. These data indicate that 2APB-induced regulation is mediated neither by Ca2+-induced Ca2+ release nor by affecting Cl− channel activity directly. We conclude that 2APB regulates the kinetics of intracellular Ca2+ signals, represented as the change in the Ca2+ oscillation patterns from brief pulsatile spikes to huge, long-lasting Ca2+waves. Moreover, this regulation seems to be mediated through InsP3-sensitive Ca2+ pools. 2APB may act as a novel, useful pharmacological tool to study the genesis of intracellular Ca2+ signals.
Footnotes
Received December 17, 1999.
Accepted August 9, 2000.
Send reprint requests to: Jie Wu, M.D., Ph.D., Division of Neurology, Barrow Neurological Institute, St. Joseph Hospital and Medical Center, 350 West Thomas Road, Phoenix AZ 85013-4496. E-mail:jwu2{at}chw.edu
↵1 Present address: Division of Neurology, Barrow Neurological Institute, St. Joseph Hospital and Medical Center, Phoenix, Arizona.
The American Society for Pharmacology and Experimental Therapeutics
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