Role of perinuclear mitochondria in the spatiotemporal dynamics of spontaneous Ca2+ waves in interstitial cells of Cajal-like cells of the rabbit urethra
Role of perinuclear mitochondria in the spatiotemporal dynamics of spontaneous Ca2+ waves in interstitial cells of Cajal-like cells of the rabbit urethra
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DOI：
10.1111/j.1476-5381.2010.00902.x
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发表时间：
2010-10-01
影响因子：
7.3
通讯作者：
Suzuki, Hikaru
中科院分区：
文献类型：
--
作者：
Hashiatni, Hikaru;Lang, Richard J.;Suzuki, Hikaru
BACKGROUND AND PURPOSEAlthough spontaneous Ca2+ waves in interstitial cells of Cajal (ICC)-like cells (ICC-LCs) primarily arise from endoplasmic reticulum (ER) Ca2+ release, the interactions among mitochondrial Ca2+ buffering, cellular energetics and ER Ca2+ release in determining the spatiotemporal dynamics of intracellular Ca2+ remain to be elucidated.EXPERIMENTAL APPROACHSpontaneous Ca2+ transients in freshly isolated ICC-LCs of the rabbit urethra were visualized using fluo-4 Ca2+ imaging, while the intracellular distribution of mitochondria was viewed with MitoTracker Red.KEY RESULTSSpontaneous Ca2+ waves invariably originated from the perinuclear region where clusters of mitochondria surround the nucleus. Perinuclear Ca2+ dynamics were characterized by a gradual rise in basal Ca2+ that preceded each regenerative Ca2+ transient. Caffeine evoked oscillatory Ca2+ waves originating from anywhere within ICC-LCs. Ryanodine or cyclopiazonic acid prevented Ca2+ wave generation with a rise in basal Ca2+, and subsequent caffeine evoked a single rudimentary Ca2+ transient. Inhibition of glycolysis with 2-deoxy-glucose or carbonyl cyanide 3-chlorophenylhydrazone, a mitochondrial protonophore, increased basal Ca2+ and abolished Ca2+ waves. However, caffeine still induced oscillatory Ca2+ transients. Mitochondrial Ca2+ uptake inhibition with RU360 attenuated Ca2+ wave amplitudes, while mitochondrial Ca2+ efflux inhibition with CGP37157 suppressed the initial Ca2+ rise to reduce Ca2+ wave frequency.CONCLUSIONS AND IMPLICATIONSPerinuclear mitochondria in ICC-LCs play a dominant role in the spatial regulation of Ca2+ wave generation and may regulate ER Ca2+ release frequency by buffering Ca2+ within microdomains between both organelles. Glycolysis inhibition reduced mitochondrial Ca2+ buffering without critically disrupting ER function. Perinuclear mitochondria may function as sensors of intracellular metabolites.
