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Is the osteoclast calcium "receptor" a receptor-operated calcium channel?
C M Bax1, V S Shankar, B S Moonga
1Department of Cellular and Molecular Sciences, St. George's Hospital Medical School, London, U.K.
Abstract:
Elevated extracellular calcium levels ([Ca2+]e) inhibit osteoclast function by elevating cytosolic free calcium levels ([Ca2+]i), presumably via the activation of a surface Ca2+ "receptor". It is unclear whether or not Ca(2+)-induced [Ca2+]i elevation involves the direct gating, by the putative "receptor", of a divalent cation channel. The results show that [Ca2+]i elevation in response to elevated [Ca2+]e comprises a distinct component of Ca2+ influx, the magnitude of which can be decreased and increased, respectively, by depolarising (100 mM-[K+]) and hyperpolarising (1 microM-[valinomycin]) the osteoclast membrane. In addition, activation of the putative Ca2+ "receptor" by elevated [Ca2+]e causes influx of the related divalent cation, magnesium (Mg2+). We suggest that Ca2+ influx induced by Ca2+ "receptor" activation is a major component of the observed [Ca2+]i response.
Insights
Elevated extracellular calcium ([Ca2+]e) triggers calcium influx into osteoclasts, a process involving a surface calcium receptor. This influx, which also allows magnesium (Mg2+) entry, is modulated by membrane potential, impacting osteoclast function.
Area of Science:
- Cell Biology
- Physiology
- Biochemistry
Background:
- Extracellular calcium ([Ca2+]e) regulates osteoclast function by altering cytosolic free calcium ([Ca2+]i).
- The precise mechanism by which calcium-sensing receptors mediate [Ca2+]i changes remains incompletely understood.
- It is unknown if the calcium receptor directly gates divalent cation channels.
Purpose of the Study:
- To investigate the role of calcium influx in calcium-induced cytosolic calcium elevation in osteoclasts.
- To determine if the putative calcium receptor directly gates ion channels.
- To explore the influence of membrane potential on calcium influx mediated by the calcium receptor.
Main Methods:
- Measurements of cytosolic free calcium ([Ca2+]i) in osteoclasts.
- Manipulation of osteoclast membrane potential using potassium (100 mM-[K+]) and valinomycin (1 microM-[valinomycin]).
- Assessment of divalent cation (Ca2+ and Mg2+) influx following calcium receptor activation.
Main Results:
- Elevated extracellular calcium ([Ca2+]e) induced a distinct component of calcium influx contributing to increased cytosolic free calcium ([Ca2+]i).
- Osteoclast membrane depolarization (100 mM-[K+]) decreased, while hyperpolarization (1 microM-[valinomycin]) increased, the magnitude of this calcium influx.
- Activation of the calcium receptor by elevated [Ca2+]e also resulted in magnesium (Mg2+) influx.
Conclusions:
- Calcium influx, mediated by the putative calcium receptor, is a significant contributor to the cytosolic free calcium ([Ca2+]i) response in osteoclasts.
- The calcium receptor appears to influence the gating of divalent cation channels, as evidenced by the modulation of calcium influx by membrane potential.
- The calcium receptor's activation leads to the influx of both calcium and magnesium ions, suggesting a broader role in divalent cation homeostasis.