Modulation of intracellular Ca2+ release and capacitative Ca2+ entry by CaMKII inhibitors in bovine vascular endothelial cells

lation of intracellular Ca2 release and capacitative Ca2 entry by CaMKII inhibitors in bovine vascular endothelial cells. Am J Physiol Cell Physiol 289: C1426–C1436, 2005. First published August 10, 2005; doi:10.1152/ajpcell.00262.2005.—The effects of inhibitors of CaMKII on intracellular Ca2 signaling were examined in single calf pulmonary artery endothelial (CPAE) cells using indo-1 microflu-orometry to measure cytoplasmic Ca2 concentration ([Ca2]i). The three CaMKII inhibitors, KN-93, KN-62, and autocamtide-2-related inhibitory peptide (AIP), all reduced the plateau phase of the [Ca2]i transient evoked by stimulation with extracellular ATP. Exposure to KN-93 or AIP alone in the presence of 2 mM extracellular Ca2 resulted in a dose-dependent increase of [Ca2]i consisting of a rapid and transient Ca2 spike followed by a small sustained plateau phase of elevated [Ca2]i. Exposure to KN-93 in the absence of extracellular Ca2 caused a transient rise of [Ca2]i, suggesting that exposure to