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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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IMCU is carried by Na+ under divalent-free conditions in skeletal muscle and heart(a) Na+ current through the MCU under divalent-free conditions (black trace), and in the presence of either 11 nM (red trace) or 160 nM (blue trace) free Ca2+ in the bath solution. Skeletal muscle (left panel), heart (right panel). Currents were normalized to membrane capacitance. The voltage protocol is shown in bottom of the figure. (b) The Na+ current through the MCU before (black trace) and after (red trace) the addition of 200 nM RuR to the bath solution. (c) Monovalent current through the MCU in symmetrical 110 mM Na+ (black trace) and after replacement of bath Na+ with K+ (red trace). (d) Histogram showing average densities of Na+ current through the MCU in skeletal muscle (n= 5) and heart (n=5). Current amplitudes were measured at 5 ms after stepping the membrane from 0 to −160 mV (see the voltage protocol). Statistical data are represented as mean ± SEM.
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Figure 4: IMCU is carried by Na+ under divalent-free conditions in skeletal muscle and heart(a) Na+ current through the MCU under divalent-free conditions (black trace), and in the presence of either 11 nM (red trace) or 160 nM (blue trace) free Ca2+ in the bath solution. Skeletal muscle (left panel), heart (right panel). Currents were normalized to membrane capacitance. The voltage protocol is shown in bottom of the figure. (b) The Na+ current through the MCU before (black trace) and after (red trace) the addition of 200 nM RuR to the bath solution. (c) Monovalent current through the MCU in symmetrical 110 mM Na+ (black trace) and after replacement of bath Na+ with K+ (red trace). (d) Histogram showing average densities of Na+ current through the MCU in skeletal muscle (n= 5) and heart (n=5). Current amplitudes were measured at 5 ms after stepping the membrane from 0 to −160 mV (see the voltage protocol). Statistical data are represented as mean ± SEM.

Mentions: Under divalent-free (DVF) conditions when bath and pipette solutions contained 110 mM Na+, we observed a quasi-linear current in both skeletal muscle and heart (Fig. 4a–c, left panels for skeletal muscle and right panels for heart throughout). This Na+ current was almost completely blocked by as low as 11 nM bath-free Ca2+, and 160 nM Ca2+ totally abolished it (Fig. 4a). The Ca2+-sensitive Na+ current was evidently mediated by the MCU that lost its selectivity under DVF conditions18, which was further confirmed by the fact that the Na+ current was completely inhibited by 200 nM RuR (Fig. 4b). Similar to COS7 cell mitoplasts18, substitution of Na+ for K+ in the bath solution resulted in significantly lower monovalent current through the MCU, showing that the MCU was relatively impermeant to K+ ions, in both skeletal muscle and heart (Fig. 4c).


Activity of the mitochondrial calcium uniporter varies greatly between tissues.

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

IMCU is carried by Na+ under divalent-free conditions in skeletal muscle and heart(a) Na+ current through the MCU under divalent-free conditions (black trace), and in the presence of either 11 nM (red trace) or 160 nM (blue trace) free Ca2+ in the bath solution. Skeletal muscle (left panel), heart (right panel). Currents were normalized to membrane capacitance. The voltage protocol is shown in bottom of the figure. (b) The Na+ current through the MCU before (black trace) and after (red trace) the addition of 200 nM RuR to the bath solution. (c) Monovalent current through the MCU in symmetrical 110 mM Na+ (black trace) and after replacement of bath Na+ with K+ (red trace). (d) Histogram showing average densities of Na+ current through the MCU in skeletal muscle (n= 5) and heart (n=5). Current amplitudes were measured at 5 ms after stepping the membrane from 0 to −160 mV (see the voltage protocol). Statistical data are represented as mean ± SEM.
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Related In: Results  -  Collection

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Figure 4: IMCU is carried by Na+ under divalent-free conditions in skeletal muscle and heart(a) Na+ current through the MCU under divalent-free conditions (black trace), and in the presence of either 11 nM (red trace) or 160 nM (blue trace) free Ca2+ in the bath solution. Skeletal muscle (left panel), heart (right panel). Currents were normalized to membrane capacitance. The voltage protocol is shown in bottom of the figure. (b) The Na+ current through the MCU before (black trace) and after (red trace) the addition of 200 nM RuR to the bath solution. (c) Monovalent current through the MCU in symmetrical 110 mM Na+ (black trace) and after replacement of bath Na+ with K+ (red trace). (d) Histogram showing average densities of Na+ current through the MCU in skeletal muscle (n= 5) and heart (n=5). Current amplitudes were measured at 5 ms after stepping the membrane from 0 to −160 mV (see the voltage protocol). Statistical data are represented as mean ± SEM.
Mentions: Under divalent-free (DVF) conditions when bath and pipette solutions contained 110 mM Na+, we observed a quasi-linear current in both skeletal muscle and heart (Fig. 4a–c, left panels for skeletal muscle and right panels for heart throughout). This Na+ current was almost completely blocked by as low as 11 nM bath-free Ca2+, and 160 nM Ca2+ totally abolished it (Fig. 4a). The Ca2+-sensitive Na+ current was evidently mediated by the MCU that lost its selectivity under DVF conditions18, which was further confirmed by the fact that the Na+ current was completely inhibited by 200 nM RuR (Fig. 4b). Similar to COS7 cell mitoplasts18, substitution of Na+ for K+ in the bath solution resulted in significantly lower monovalent current through the MCU, showing that the MCU was relatively impermeant to K+ ions, in both skeletal muscle and heart (Fig. 4c).

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