Nuclear Ca2+ sparks and waves mediated by inositol 1,4,5-trisphosphate receptors in neonatal rat cardiomyocytes

Dynamic nuclear Ca2+ signals play pivotal roles in diverse cellular functions including gene transcription, cell growth, differentiation, and apoptosis. Here we report a novel nuclear Ca2+ regulatory mechanism mediated by mositol 1,4,5-trispliosphate receptors (IP(3)Rs) around the nucleus in developing cardiac myocytes. Activation Of IP(3)Rs by alpha(1)-adrenergic receptor (alpha(1)AR) stimulation or by IP3 application (in saponinpermeabilized cells) increases Ca2+ spark frequency preferentially in the region around the nucleus in neonatal rat ventricular myocytes. A nuclear enrichment Of IP3R distribution supports the higher responsiveness of Ca2+ release in this particular region. Strikingly, we observed "nuclear Ca2+ waves" that engulf the entire nucleus without spreading into the bulk cytosol. alpha(1)AR stimulation enhances the occurrence of nuclear Ca2+ waves and confers them the ability to trigger cytosolic Ca2+ waves via IP3R-dependent pathways. This finding accounts, at least partly, for a profound frequency-dependent modulation of global Ca2+ oscillations during alpha(1) AR stimulation. Thus, IP3R-mediated Ca2+ waves traveling in the nuclear region provide active, autonomous regulation of nuclear Ca2+ signaling, which provides for not only the local signal transduction, but also a pacemaker to drive global Ca2+ transient in the context of alpha(1)AR stimulation in developing cardiac myocytes. (C) 2007 Elsevier Ltd. All rights reserved.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000254158600006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Cell BiologySCI(E)45ARTICLE2165-1744