Chloride (Cl-) channels participate in the regulation of cardiac function in response to stress although the underlying regulatory
mechanism remains poorly understood. This study was designed to examine the impact of the pro-apoptotic stimulus staurosporine (STS)
on the volume-sensitive outwardly rectifying Cl- current (ICl,Vol) in cardiomyocytes and possible regulatory mechanism involved with a
focus on phosphatidylinositol-3 kinase (PI3K)/Akt. Primary cultured rat neonatal cardiomyocytes were subjected to hypotonic and isotonic
environment in the presence or absence of STS prior to whole-cell voltage-clamp evaluation of Cl- current. Whole-cell recordings
revealed that STS activated an outwardly rectifying Cl- current with phenotypic properties reminiscent of ICl,Vol. These currents were outwardly
rectifying with a time-dependent inactivation at positive potentials and were sensitive to 4,4'-diisothiocya-natostilbene- 2,2'-
disulfonicacid (DIDS), a non-selective Cl- channel blocker, and 4-(2-butyl-6,7-dichlor-2-cyclopentyl-indan-1-on-5-yl)oxybutyric acid
(DCPIB), a selective VSOR Cl- channel blocker. DIDS and DCPIB inhibited ICl,Vol by 92.6% ± 7.3% and 78.4% ± 5.5%, respectively.
Our data further revealed that the PI3K inhibitor LY294002 facilitated the current with the peak amplitude of 19.54 ± 2.70 pA/pF. To the
contrary, insulin partially inhibited the current amplitude with the peak current amplitude of 15.4 ± 2.13 pA/pF. Taken together, our data
depicted staurosporine is capable of activating ICl,Vol channel in cardiomyocytes via possibly a PI3K/Akt-dependent mechanism.