JCB logo
amgmicro.com
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 371K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Babcock, D. F.
Right arrow Articles by Hille, B.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Babcock, D. F.
Right arrow Articles by Hille, B.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

© The Rockefeller University Press, 0021-9525/1997//833 $5.00
The Journal of Cell Biology, Volume 136, Number 4, , 1997 833-844

Article

Mitochondrial Participation in the Intracellular Ca2+ Network



Donner F. Babcock, James Herrington, Paul C. Goodwin*, Young Bae Park, and Bertil Hille

Department of Physiology & Biophysics, University of Washington, Seattle, Washington 98195-7290; and * Image Analysis Laboratory, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104

Calcium can activate mitochondrial metabolism, and the possibility that mitochondrial Ca2+ uptake and extrusion modulate free cytosolic [Ca2+] (Cac) now has renewed interest. We use whole-cell and perforated patch clamp methods together with rapid local perfusion to introduce probes and inhibitors to rat chromaffin cells, to evoke Ca2+ entry, and to monitor Ca2+-activated currents that report near-surface [Ca2+]. We show that rapid recovery from elevations of Cac requires both the mitochondrial Ca2+ uniporter and the mitochondrial energization that drives Ca2+ uptake through it. Applying imaging and single-cell photometric methods, we find that the probe rhod-2 selectively localizes to mitochondria and uses its responses to quantify mitochondrial free [Ca2+] (Cam). The indicated resting Cam of 100–200 nM is similar to the resting Cac reported by the probes indo-1 and Calcium Green, or its dextran conjugate in the cytoplasm. Simultaneous monitoring of Cam and Cac at high temporal resolution shows that, although Cam increases less than Cac, mitochondrial sequestration of Ca2+ is fast and has high capacity. We find that mitochondrial Ca2+ uptake limits the rise and underlies the rapid decay of Cac excursions produced by Ca2+ entry or by mobilization of reticular stores. We also find that subsequent export of Ca2+ from mitochondria, seen as declining Cam, prolongs complete Cac recovery and that suppressing export of Ca2+, by inhibition of the mitochondrial Na+/ Ca2+ exchanger, reversibly hastens final recovery of Cac. We conclude that mitochondria are active participants in cellular Ca2+ signaling, whose unique role is determined by their ability to rapidly accumulate and then release large quantities of Ca2+.

Abbreviations used in this paper: Cac, free cytosolic [Ca2+]; Cam, free intramitochondrial [Ca2+]; CGP-37157, 7-chloro-3,5-dihydro-5-phenyl-1H4,1-benzothiazepine-2-on; BHQ, 2,5 di(t-butyl)-1,4-hydroxyquinone; CCCP, carbonyl cyanide m-chlorophenylhydrazone.

Please address all correspondence to B. Hille, Department of Physiology & Biophysics, G424 Health Sciences Building, University of Washington, Box 357290, Seattle, WA 98195-7290. Tel.: (206) 543-8639. Fax: (206) 6850619. E-Mail: hille{at}u.washington.edu


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents