PT  - JOURNAL ARTICLE
AU  - David R. Giovannucci
AU  - Michael D. Hlubek
AU  - Edward L. Stuenkel
TI  - Mitochondria Regulate the Ca<sup>2+</sup>–Exocytosis Relationship of Bovine Adrenal Chromaffin Cells
AID  - 10.1523/JNEUROSCI.19-21-09261.1999
DP  - 1999 Nov 01
TA  - The Journal of Neuroscience
PG  - 9261--9270
VI  - 19
IP  - 21
4099  - http://www.jneurosci.org/content/19/21/9261.short
4100  - http://www.jneurosci.org/content/19/21/9261.full
SO  - J. Neurosci.1999 Nov 01; 19
AB  - The present study expands the contemporary view of mitochondria as important participants in cellular Ca2+ dynamics and provides evidence that mitochondria regulate the supply of release-competent secretory granules. Using pharmacological probes to inhibit mitochondrial Ca2+ import, the ability of mitochondria to modulate secretory activity in single, patch-clamped bovine chromaffin cells was examined by simultaneously monitoring rapid changes in membrane surface area (ΔCm) and cytosolic Ca2+ levels ([Ca2+]c). Repetitive step depolarizations or action potential waveforms were found to raise the [Ca2+]c of chromaffin cells into the 1 μm to tens of micromolar range. Inhibiting mitochondria by treatment with carbonyl cyanidep-(trifuoro-methoxy)phenylhydrazone, antimycin–oligomycin, or ruthenium red revealed that mitochondria are a prominent component for the clearance of Ca2+ that entered via voltage-activated Ca2+ channels. Disruption of cellular Ca2+ homeostasis by poisoning mitochondria enhanced the secretory responsiveness of chromaffin cells by increasing the amplitude of the transient rise and the time course of recovery to baseline of the evoked Δ[Ca2+]c. The enhancement of the secretory response was represented by significant deviation of the Ca2+–exocytosis relationship from a standard relationship that equates Ca2+ influx and ΔCm. Thus, mitochondria would play a critical role in the control of secretory activity in chromaffin cells that undergo tonic or repetitive depolarizing activity, likely by limiting the Ca2+-dependent activation of specific proteins that recruit or prime secretory granules for exocytosis.