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Role of perinuclear mitochondria in the spatiotemporal dynamics of spontaneous Ca 2+ waves in interstitial cells of Cajal‐like cells of the rabbit urethra
Author(s) -
Hashiatni Hikaru,
Lang Richard J,
Suzuki Hikaru
Publication year - 2010
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.00902.x
Subject(s) - interstitial cell of cajal , mitochondrion , urethra , dynamics (music) , microbiology and biotechnology , anatomy , biology , pathology , chemistry , biophysics , physics , smooth muscle , medicine , endocrinology , acoustics
BACKGROUND AND PURPOSE Although spontaneous Ca 2+ waves in interstitial cells of Cajal (ICC)‐like cells (ICC‐LCs) primarily arise from endoplasmic reticulum (ER) Ca 2+ release, the interactions among mitochondrial Ca 2+ buffering, cellular energetics and ER Ca 2+ release in determining the spatiotemporal dynamics of intracellular Ca 2+ remain to be elucidated. EXPERIMENTAL APPROACH Spontaneous Ca 2+ transients in freshly isolated ICC‐LCs of the rabbit urethra were visualized using fluo‐4 Ca 2+ imaging, while the intracellular distribution of mitochondria was viewed with MitoTracker Red. KEY RESULTS Spontaneous Ca 2+ waves invariably originated from the perinuclear region where clusters of mitochondria surround the nucleus. Perinuclear Ca 2+ dynamics were characterized by a gradual rise in basal Ca 2+ that preceded each regenerative Ca 2+ transient. Caffeine evoked oscillatory Ca 2+ waves originating from anywhere within ICC‐LCs. Ryanodine or cyclopiazonic acid prevented Ca 2+ wave generation with a rise in basal Ca 2+ , and subsequent caffeine evoked a single rudimentary Ca 2+ transient. Inhibition of glycolysis with 2‐deoxy‐glucose or carbonyl cyanide 3‐chlorophenylhydrazone, a mitochondrial protonophore, increased basal Ca 2+ and abolished Ca 2+ waves. However, caffeine still induced oscillatory Ca 2+ transients. Mitochondrial Ca 2+ uptake inhibition with RU360 attenuated Ca 2+ wave amplitudes, while mitochondrial Ca 2+ efflux inhibition with CGP37157 suppressed the initial Ca 2+ rise to reduce Ca 2+ wave frequency. CONCLUSIONS AND IMPLICATIONS Perinuclear mitochondria in ICC‐LCs play a dominant role in the spatial regulation of Ca 2+ wave generation and may regulate ER Ca 2+ release frequency by buffering Ca 2+ within microdomains between both organelles. Glycolysis inhibition reduced mitochondrial Ca 2+ buffering without critically disrupting ER function. Perinuclear mitochondria may function as sensors of intracellular metabolites.