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

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• 作者：Dali Luo ; Dongmei Yang ; Xiaomei Lan ; Kaitao Li ; Xiaodong Li ; Ju Chen ; Youyi Zhang ; Rui-Ping Xiao ; Qide Han ; Heping Cheng
• 关键词：Cardiomyocytes ; Nuclear Ca²⁺ signaling ; Inositol 1 ; 4 ; 5-trisphosphate receptors ; Ca²⁺ sparks ; α ; ₁ adrenergic stimulation
• 刊名：Cell Calcium
• 出版年：2008
• 出版时间：February 2008
• 年：2008
• 卷：43
• 期：2
• 页码：165-174
• 全文大小：1496 K

文摘

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 inositol 1,4,5-trisphosphate receptors (IP₃Rs) around the nucleus in developing cardiac myocytes. Activation of IP₃Rs by α₁-adrenergic receptor (α₁AR) stimulation or by IP₃ application (in saponin-permeabilized 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. α₁AR 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 α₁AR 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 α₁AR stimulation in developing cardiac myocytes.