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
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.
Digital Object Identifier (DOI)
Wu, Jie; Kamimura, Noritaka; Takeo, Teruko; Suga, Sechiko; Wakui, Makoto; Maruyama, Takayuki; and Mikoshiba, Katsuhiko, "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" (2000). Translational Neuroscience. 399.