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Activity of the mitochondrial calcium uniporter varies greatly between tissues.

Fieni F, Lee SB, Jan YN, Kirichok Y - Nat Commun (2012)

Bottom Line: Similarly, in Drosophila flight muscle, mitochondrial calcium uniporter activity is barely detectable compared with that in other fly tissues.As mitochondria occupy up to 40% of the cell volume in highly metabolically active heart and flight muscle, low mitochondrial calcium uniporter activity is likely essential to avoid cytosolic Ca(2+) sink due to excessive mitochondrial Ca(2+) uptake.Simultaneously, low mitochondrial calcium uniporter activity may also prevent mitochondrial Ca(2+) overload in such active tissues exposed to frequent cytosolic Ca(2+) activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of California, San Francisco, San Francisco, California 94158, USA.

ABSTRACT
The mitochondrial calcium uniporter is a highly selective channel responsible for mitochondrial Ca(2+) uptake. The mitochondrial calcium uniporter shapes cytosolic Ca(2+) signals, controls mitochondrial ATP production, and is involved in cell death. Here using direct patch-clamp recording from the inner mitochondrial membrane, we compare mitochondrial calcium uniporter activity in mouse heart, skeletal muscle, liver, kidney and brown fat. Surprisingly, heart mitochondria show a dramatically lower mitochondrial calcium uniporter current density than the other tissues studied. Similarly, in Drosophila flight muscle, mitochondrial calcium uniporter activity is barely detectable compared with that in other fly tissues. As mitochondria occupy up to 40% of the cell volume in highly metabolically active heart and flight muscle, low mitochondrial calcium uniporter activity is likely essential to avoid cytosolic Ca(2+) sink due to excessive mitochondrial Ca(2+) uptake. Simultaneously, low mitochondrial calcium uniporter activity may also prevent mitochondrial Ca(2+) overload in such active tissues exposed to frequent cytosolic Ca(2+) activity.

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Divalent cation permeability of IMCU in skeletal muscle and heart(a) Representative IMCU recorded in the presence of different concentrations of Ca2+ in the bath: nominal Ca2+-free (black), 50 μM (red), 100 μM (blue), and 1 mM (green). Voltage-ramp protocol is indicated on top. (b) Left panel, Representative IMCU recorded from a skeletal muscle mitoplast in the presence of 100 μM Ca2+ (red trace), Ba2+ (black trace), and Mg2+ (blue trace). Right panel, Representative IMCU recorded from a heart mitoplast in the presence of 1 mM Ca2+ (red trace), Ba2+ (black trace), and Mg2+ (blue trace). (c) Histograms of the relative permeability of IMCU to Ca2+, Ba2+, and Mg2+ in skeletal muscle (n=4, left panel) and heart (n=4, right panel). Current amplitudes were measured at 5 ms after stepping from 0 to −160 mV (see the voltage protocol in b). Statistical data are represented as mean ± SEM.
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Figure 3: Divalent cation permeability of IMCU in skeletal muscle and heart(a) Representative IMCU recorded in the presence of different concentrations of Ca2+ in the bath: nominal Ca2+-free (black), 50 μM (red), 100 μM (blue), and 1 mM (green). Voltage-ramp protocol is indicated on top. (b) Left panel, Representative IMCU recorded from a skeletal muscle mitoplast in the presence of 100 μM Ca2+ (red trace), Ba2+ (black trace), and Mg2+ (blue trace). Right panel, Representative IMCU recorded from a heart mitoplast in the presence of 1 mM Ca2+ (red trace), Ba2+ (black trace), and Mg2+ (blue trace). (c) Histograms of the relative permeability of IMCU to Ca2+, Ba2+, and Mg2+ in skeletal muscle (n=4, left panel) and heart (n=4, right panel). Current amplitudes were measured at 5 ms after stepping from 0 to −160 mV (see the voltage protocol in b). Statistical data are represented as mean ± SEM.

Mentions: As expected for the Ca2+ current, IMCU gradually increased as Ca2+ concentrations in the bath were gradually elevated from 50 μM to 1 mM in both heart and skeletal muscle (Fig. 3a). Mg2+ did not induce any IMCU (Fig. 3b), and the current traces in the presence of Mg2+ in the bath solution were identical to the baseline (obtained in 200 nM RuR, data not shown). The addition of Ba2+ to the bath induced IMCU, but the Ba2+ current was much smaller than that induced by Ca2+ (Fig. 3b and c). The permeability sequence for IMCU, Ca2+ ≫ Ba2+ > Mg2+, (Fig. 3c) was the same as reported for the MCU studied by indirect methods17,33,34 and by patch-clamping mitoplasts from COS7 cells18. Notably, the IMCU permeability sequence is unique, as most Ca2+ channels conduct Ba2+ better than Ca2+ (35).


Activity of the mitochondrial calcium uniporter varies greatly between tissues.

Fieni F, Lee SB, Jan YN, Kirichok Y - Nat Commun (2012)

Divalent cation permeability of IMCU in skeletal muscle and heart(a) Representative IMCU recorded in the presence of different concentrations of Ca2+ in the bath: nominal Ca2+-free (black), 50 μM (red), 100 μM (blue), and 1 mM (green). Voltage-ramp protocol is indicated on top. (b) Left panel, Representative IMCU recorded from a skeletal muscle mitoplast in the presence of 100 μM Ca2+ (red trace), Ba2+ (black trace), and Mg2+ (blue trace). Right panel, Representative IMCU recorded from a heart mitoplast in the presence of 1 mM Ca2+ (red trace), Ba2+ (black trace), and Mg2+ (blue trace). (c) Histograms of the relative permeability of IMCU to Ca2+, Ba2+, and Mg2+ in skeletal muscle (n=4, left panel) and heart (n=4, right panel). Current amplitudes were measured at 5 ms after stepping from 0 to −160 mV (see the voltage protocol in b). Statistical data are represented as mean ± SEM.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3818247&req=5

Figure 3: Divalent cation permeability of IMCU in skeletal muscle and heart(a) Representative IMCU recorded in the presence of different concentrations of Ca2+ in the bath: nominal Ca2+-free (black), 50 μM (red), 100 μM (blue), and 1 mM (green). Voltage-ramp protocol is indicated on top. (b) Left panel, Representative IMCU recorded from a skeletal muscle mitoplast in the presence of 100 μM Ca2+ (red trace), Ba2+ (black trace), and Mg2+ (blue trace). Right panel, Representative IMCU recorded from a heart mitoplast in the presence of 1 mM Ca2+ (red trace), Ba2+ (black trace), and Mg2+ (blue trace). (c) Histograms of the relative permeability of IMCU to Ca2+, Ba2+, and Mg2+ in skeletal muscle (n=4, left panel) and heart (n=4, right panel). Current amplitudes were measured at 5 ms after stepping from 0 to −160 mV (see the voltage protocol in b). Statistical data are represented as mean ± SEM.
Mentions: As expected for the Ca2+ current, IMCU gradually increased as Ca2+ concentrations in the bath were gradually elevated from 50 μM to 1 mM in both heart and skeletal muscle (Fig. 3a). Mg2+ did not induce any IMCU (Fig. 3b), and the current traces in the presence of Mg2+ in the bath solution were identical to the baseline (obtained in 200 nM RuR, data not shown). The addition of Ba2+ to the bath induced IMCU, but the Ba2+ current was much smaller than that induced by Ca2+ (Fig. 3b and c). The permeability sequence for IMCU, Ca2+ ≫ Ba2+ > Mg2+, (Fig. 3c) was the same as reported for the MCU studied by indirect methods17,33,34 and by patch-clamping mitoplasts from COS7 cells18. Notably, the IMCU permeability sequence is unique, as most Ca2+ channels conduct Ba2+ better than Ca2+ (35).

Bottom Line: Similarly, in Drosophila flight muscle, mitochondrial calcium uniporter activity is barely detectable compared with that in other fly tissues.As mitochondria occupy up to 40% of the cell volume in highly metabolically active heart and flight muscle, low mitochondrial calcium uniporter activity is likely essential to avoid cytosolic Ca(2+) sink due to excessive mitochondrial Ca(2+) uptake.Simultaneously, low mitochondrial calcium uniporter activity may also prevent mitochondrial Ca(2+) overload in such active tissues exposed to frequent cytosolic Ca(2+) activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of California, San Francisco, San Francisco, California 94158, USA.

ABSTRACT
The mitochondrial calcium uniporter is a highly selective channel responsible for mitochondrial Ca(2+) uptake. The mitochondrial calcium uniporter shapes cytosolic Ca(2+) signals, controls mitochondrial ATP production, and is involved in cell death. Here using direct patch-clamp recording from the inner mitochondrial membrane, we compare mitochondrial calcium uniporter activity in mouse heart, skeletal muscle, liver, kidney and brown fat. Surprisingly, heart mitochondria show a dramatically lower mitochondrial calcium uniporter current density than the other tissues studied. Similarly, in Drosophila flight muscle, mitochondrial calcium uniporter activity is barely detectable compared with that in other fly tissues. As mitochondria occupy up to 40% of the cell volume in highly metabolically active heart and flight muscle, low mitochondrial calcium uniporter activity is likely essential to avoid cytosolic Ca(2+) sink due to excessive mitochondrial Ca(2+) uptake. Simultaneously, low mitochondrial calcium uniporter activity may also prevent mitochondrial Ca(2+) overload in such active tissues exposed to frequent cytosolic Ca(2+) activity.

Show MeSH
Related in: MedlinePlus