Modulation of Ca 2+ ‐activated Cl − currents in rabbit portal vein smooth muscle by an inhibitor of mitochondrial Ca 2+ uptake
The effects of carbonyl cyanide m ‐chlorophenyl hydrazone (CCCP), an inhibitor of mitochondrial Ca 2+ uptake, was investigated on the properties of Ca 2+ ‐activated chloride currents ( I Cl(Ca) ) in rabbit portal vein smooth muscle cells using the perforated patch whole‐cell voltage‐clamp technique...
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| Published in | The Journal of physiology Vol. 505; no. 1; pp. 53 - 64 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
01.11.1997
|
| Online Access | Get full text |
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| Summary: | The effects of carbonyl cyanide
m
‐chlorophenyl hydrazone (CCCP), an inhibitor of mitochondrial Ca
2+
uptake, was investigated on the properties of Ca
2+
‐activated chloride currents (
I
Cl(Ca)
) in rabbit portal vein smooth muscle cells using the perforated patch whole‐cell voltage‐clamp technique to ascertain whether this Ca
2+
uptake process influences the time course of the subsarcolemmal Ca
2+
signal that activates
I
Cl(Ca)
.
In cells bathed in either physiological calcium (2 m
m
Ca
2+
o
) or high calcium (10 mm Ca
2+
o
) external solutions, application of CCCP (1–2 μ
m
) evoked an inward current and prolonged the exponential decay time constant (τ) of Ca
2+
‐activated Cl
−
‘tail’ currents (
I
tall
) evoked by Ca
2+
influx through voltage‐dependent calcium channels (VDCCs). The effect of CCCP on τ was greater in cells where the amplitude of
I
tall
was relatively large and, in different cells, the effect of CCCP on
T
was positively correlated with the amplitude of
I
tall
.
CCCP abolished spontaneously occurring transient Ca
2+
‐activated Cl
−
currents (STICs), but did not alter their time course before complete block.
Thapsigargin and cyclopiazonic acid (inhibitors of the sarcoplasmic Ca
2+
‐ATPase) inhibited STICs, but did not affect the decay of
I
tall
or STICs.
In conclusion, when Ca
2+
enters the cell through VDCCs, the time course of the consequent Ca
2+
signal in the subsarcolemmal domain containing Ca
2+
‐activated chloride channels appears to be regulated by Ca
2+
uptake into mitochondria. In contrast, inhibition of Ca
2+
uptake by the sarcoplasmic reticulum ATPase does not seem to influence the time course of
I
Cl(Ca)
. |
|---|---|
| ISSN: | 0022-3751 1469-7793 |
| DOI: | 10.1111/j.1469-7793.1997.053bc.x |