Title

2-Aminoethoxydiphenyl Borate Modulates Kinetics Of Intracellular Ca 2+ Signals Mediated By Inositol 145-Trisphosphate-Sensitive Ca 2+ Stores In Single Pancreatic Acinar Cells Of Mouse

Department

neurobiology

Document Type

Article

Abstract

Regulation of the kinetics of intracellular Ca 2+ signals with a novel, membrane-penetrable, inositol 1,4,5-trisphosphate (InsP 3 ) receptor/Ca 2+ channel modulator, 2-amino-ethoxydiphenyl borate (2APB), has been investigated using patchclamp, whole-cell recording to monitor Ca 2+ -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 Ca 2+ release from pulsatile spikes to long-lasting, huge Ca 2+ waves, suggesting that 2APB coordinates local Ca 2+ release to generate global Ca 2+ signals. The regulation by 2APB can be elicited by internal perfusion of InsP 3 in a concentration-dependent manner, indicating that this regulation is not mediated through membrane receptors or G protein signal transduction. The InsP 3 receptor blocker heparin, but not the ryanodine-sensitive receptor blockers ruthenium red or ryanodine, abolishes 2APB-mediated regulation of Ca 2+ release. This results also suggest that 2APB effects are mediated through InsP 3 receptors. 2APB substantially modifies single inward Cl - current pulse evoked by the photolytic release of caged InsP 3 but not by caged Ca 2+ . These data indicate that 2APB-induced regulation is mediated neither by Ca 2+ -induced Ca 2+ release nor by affecting Cl - channel activity directly. We conclude that 2APB regulates the kinetics of intracellular Ca 2+ signals, represented as the change in the Ca 2+ oscillation patterns from brief pulsatile spikes to huge, long-lasting Ca 2+ waves. Moreover, this regulation seems to be mediated through InsP 3 -sensitive Ca 2+ pools. 2APB may act as a novel, useful pharmacological tool to study the genesis of intracellular Ca 2+ signals.

Publication Date

1-1-2000

Publication Title

Molecular Pharmacology

ISSN

0026895X

Volume

58

Issue

6

First Page

1368

Last Page

1374

Digital Object Identifier (DOI)

10.1124/mol.58.6.1368

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