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Protection of TRPC7 cation channels from calcium inhibition by closely associated SERCA pumps

Loïc Lemonnier1, Mohamed Trebak, Jean-Philippe Lievremont

  • 1National Institute of Environmental Health Sciences, NIH, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|January 13, 2006
PubMed

Insights

Transient Receptor Potential (TRP) channels, like TRPC7, are regulated by calcium. This study reveals a novel negative feedback mechanism where calcium entry through TRPC7 channels inhibits their own activation.

Area of Science:

  • Cellular Physiology
  • Ion Channel Regulation
  • Calcium Signaling

Background:

  • Transient Receptor Potential (TRP) channels mediate regulated calcium (Ca2+) entry.
  • Ca2+-permeable channels often exhibit complex Ca2+-dependent regulation.
  • TRPC7 channels are activated by diacylglycerols and store-operated mechanisms.

Purpose of the Study:

  • To investigate the regulation of TRPC7 channel activity.
  • To elucidate the mechanism by which SERCA pump inhibition affects TRPC7 activation.
  • To identify novel calcium-dependent regulatory pathways for TRPC channels.

Main Methods:

  • Investigated TRPC7 and TRPC3 channel activity in response to diacylglycerol stimulation.
  • Utilized the SERCA pump inhibitor thapsigargin to assess its effect on channel activation.
  • Examined the role of extracellular calcium, calcium influx, calmodulin, and actin cytoskeleton.

Main Results:

  • Thapsigargin blocked diacylglycerol-induced activation of TRPC7 and TRPC3 channels.
  • This inhibition was dependent on extracellular calcium and the driving force for Ca2+ entry.
  • The effect was mediated by calcium entry through TRPC7 channels, not store-operated channels, and involved calmodulin and the actin cytoskeleton.

Conclusions:

  • A novel negative feedback mechanism regulates TRPC channels, where calcium influx inhibits channel activity.
  • This calcium-mediated inhibition is attenuated by associated SERCA pumps under physiological conditions.
  • Findings reveal a new layer of complexity in TRPC channel regulation by intracellular calcium dynamics.

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