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Ca(2+) influx through the osteoclastic plasma membrane ryanodine receptor
Baljit S Moonga1, Sun Li, Jameel Iqbal
1Mount Sinai Bone Program, Department of Medicine, Mount Sinai School of Medicine, Bronx Veterans Affairs Medical Center, New York 10029, USA.
American Journal of Physiology. Renal Physiology
|April 6, 2002
Summary
The type 2 ryanodine receptor (RyR-2) in osteoclasts acts as a calcium channel and sensor. It controls calcium influx and detects extracellular calcium levels, influencing bone cell function.
Area of Science:
- Cell Biology
- Ion Channel Physiology
- Bone Biology
Background:
- Osteoclasts are crucial for bone resorption.
- Calcium signaling is vital for osteoclast function.
- The role of RyR-2 in osteoclast membrane calcium transport is not fully understood.
Purpose of the Study:
- To investigate the function of RyR-2 in osteoclast membrane as a Ca(2+) influx channel and divalent cation sensor.
- To determine the location of the divalent cation sensing site (extracellular vs. intracellular).
Main Methods:
- Cytosolic Ca(2+) measurements in osteoclasts.
- Single-channel recordings from excised membrane patches.
- Protease protection assays using pronase.
- Inhibition studies with specific antibodies (Ab(34)).
Main Results:
- RyR-2 mediates Ca(2+) influx at depolarized membrane potentials.
- Ryanodine modulates extracellular Ca(2+) influx.
- Single-channel recordings show a divalent cation-selective conductance sensitive to RyR modulators.
- Extracellular application of divalent cations triggers Ca(2+) signals, which are blocked by pronase treatment of the cell surface.
- Intracellular antibody application inhibits divalent cation sensing.
Conclusions:
- RyR-2 functions as a membrane-resident Ca(2+) influx channel in osteoclasts.
- RyR-2 possesses an extracellular divalent cation activation site.
- RyR-2 acts as a sensor for extracellular divalent cations, regulating Ca(2+) influx.