Cell membrane stretch in osteoclasts triggers a self-reinforcing Ca2+ entry pathway

Area of Science:

• Cell Biology
• Biophysics
• Physiology

Background:

• Cellular responses to mechanical stimuli are crucial for physiological functions.
• Stretch-activated (SA) ion channels are implicated in mechanotransduction pathways.
• Osteoclasts play a key role in bone remodeling and resorption.

Purpose of the Study:

• To investigate the mechanisms of cell membrane stretch-evoked responses in fetal chicken osteoclasts.
• To elucidate the role of SA and Ca2+-activated K+ (KCa) channels in these responses.
• To understand the self-reinforcing feedback loop involving ion channel activity and intracellular calcium.

Main Methods:

• Patch-clamp electrophysiology to measure ion channel activity and membrane potential.
• Ca2+ imaging to monitor intracellular Ca2+ ([Ca2+]i) changes.
• Simultaneous patch-clamp and Ca2+ imaging measurements in fetal chicken osteoclasts.

Main Results:

• Mechanical membrane stretch induced intracellular Ca2+ responses in osteoclasts.
• Both SA and KCa channels were activated near resting membrane potential during stretch.
• SA channels are permeable to Ca2+, and their activity, coupled with KCa channel-mediated hyperpolarization, creates a positive feedback loop.
• This mechanism leads to Ca2+ waves and cell membrane hyperpolarization, which ceases upon removal of stretch.

Conclusions:

• A self-reinforcing mechanism involving SA and KCa channels regulates Ca2+ influx and membrane potential changes in osteoclasts.
• This Ca2+ entry pathway is crucial for osteoclast mechanosensing and may play a role in regulating osteoclast function.
• The findings provide insights into the biophysical basis of osteoclast mechanotransduction.