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This Article Full Text Full Text (PDF) All Versions of this Article: 586/19/4609    most recent jphysiol.2008.157990v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Royer, L. Articles by Ríos, E. PubMed PubMed Citation Articles by Royer, L. Articles by Ríos, E. Related Collections Cellular

¹ Section of Cellular Signalling, Department of Molecular Biophysics & Physiology, Rush University, 1750 W. Harrison St, Chicago, IL 60612, USA
² Physiologie Intégrative Cellulaire et Moléculaire, Université Claude Bernard Lyon 1, UMR CNRS 5123, Bâtiment Raphael Dubois, 43 boulevard du 11 novembre 1918, F 69622 Villeurbanne Cedex, France

Intracellular calcium signals regulate multiple cellular functions. They depend on release of Ca²⁺ from cellular stores into the cytosol, a process that in many types of cells appears to be tightly controlled by changes in [Ca²⁺] within the store. In contrast with cardiac muscle, where depletion of Ca²⁺ in the sarcoplasmic reticulum is a crucial determinant of termination of Ca²⁺ release, in skeletal muscle there is no agreement regarding the sign, or even the existence of an effect of SR Ca²⁺ level on Ca²⁺ release. To address this issue we measured Ca²⁺ transients in mouse flexor digitorum brevis (FDB) skeletal muscle fibres under voltage clamp, using confocal microscopy and the Ca²⁺ monitor rhod-2. The evolution of Ca²⁺ release flux was quantified during long-lasting depolarizations that reduced severely the Ca²⁺ content of the SR. As in all previous determinations in mammals and non-mammals, release flux consisted of an early peak, relaxing to a lower level from which it continued to decay more slowly. Decay of flux in this second stage, which has been attributed largely to depletion of SR Ca²⁺, was studied in detail. A simple depletion mechanism without change in release permeability predicts an exponential decay with time. In contrast, flux decreased non-exponentially, to a finite, measurable level that could be maintained for the longest pulses applied (1.8 s). An algorithm on the flux record allowed us to define a quantitative index, the normalized flux rate of change (NFRC), which was shown to be proportional to the ratio of release permeability P and inversely proportional to Ca²⁺ buffering power B of the SR, thus quantifying the ‘evacuability’ or ability of the SR to empty its content. When P and B were constant, flux then decayed exponentially, and NFRC was equal to the exponential rate constant. Instead, in most cases NFRC increased during the pulse, from a minimum reached immediately after the early peak in flux, to a time between 200 and 250 ms, when the index was no longer defined. NFRC increased by 111% on average (in 27 images from 18 cells), reaching 300% in some cases. The increase may reflect an increase in P, a decrease in B, or both. On experimental and theoretical grounds, both changes are to be expected upon SR depletion. A variable evacuability helps maintain a constant Ca²⁺ output under conditions of diminishing store Ca²⁺ load.

(Received 6 June 2008; accepted after revision 6 August 2008; first published online 7 August 2008)
Corresponding author E. Ríos: Section of Cellular Signalling, Department of Molecular Biophysics & Physiology, Rush University School of Medicine, 1750 W. Harrison St. Suite 1279JS, Chicago, IL 60612, USA.  Email: erios{at}rush.edu