TRPC6 regulates cell cycle progression by modulating membrane potential in bone marrow stromal cells.

Area of Science:

• Cell Biology
• Calcium Signaling
• Regenerative Medicine

Background:

• Calcium ion (Ca2+) influx is crucial for cell cycle progression.
• Mechanisms of Ca2+ influx vary across cell types.
• Transient Receptor Potential (TRP) channels and store-operated Ca2+ entry (SOCE) molecules STIM/Orai are investigated for their roles.

Purpose of the Study:

• To investigate the roles of TRP channels and SOCE-related molecules (STIM/Orai) in rat bone marrow stromal cell (BMSC) cycle progression.
• To understand the specific contributions of TRPC1 and TRPC6 channels in BMSC proliferation.

Main Methods:

• Utilized PCR and immunoblotting for gene and protein expression analysis.
• Employed fluorescence imaging and patch clamping for Ca2+ influx and membrane potential measurements.
• Conducted flow cytometry for cell cycle analysis and siRNA knockdown experiments.

Main Results:

• S phase-specific enhancement of TRPC1, STIM, and Orai expression observed.
• TRPC6 expression inversely correlated with cell cycle phases (decreased in S, increased in G1).
• TRPC6 knockdown led to increased SOCE, altered membrane potential, and promoted BMSC proliferation through S and G2/M phases.

Conclusions:

• TRPC6 plays a key role in regulating SOCE magnitude by altering membrane potential, which is critical for BMSC cell cycle progression.
• Modulating TRPC6 offers a potential therapeutic strategy for controlling BMSC proliferation.
• Findings contribute to understanding calcium signaling in regenerative medicine.