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Transient receptor potential canonical type 1 (TRPC1) operates as a sarcoplasmic reticulum calcium leak channel in

Céline Berbey1, Norbert Weiss1, Claude Legrand1

  • 1Laboratoire de Physiologie Intégrative, Cellulaire, et Moléculaire, Université de Lyon, Université Lyon 1, CNRS Unité Mixte de Recherche 5123, 69622 Villeurbanne Cedex, France.

The Journal of Biological Chemistry
|October 31, 2009
PubMed

Insights

Type 1 transient receptor potential canonical (TRPC1) channels function as sarcoplasmic reticulum (SR) Ca(2+) leak channels in skeletal muscle, not plasma membrane influx channels as previously hypothesized. This finding impacts understanding of muscle calcium regulation.

Area of Science:

  • Muscle physiology
  • Ion channel function
  • Calcium signaling

Background:

  • Type 1 transient receptor potential canonical (TRPC1) channels are known to function in nonexcitable cells, primarily in plasma membranes, activated by various stimuli.
  • In skeletal muscle, TRPC1's role is hypothesized to involve sarcolemmal calcium influx, but direct evidence is lacking.

Purpose of the Study:

  • To investigate the functional role and localization of TRPC1 channels in adult mouse skeletal muscle fibers.
  • To determine if TRPC1 channels mediate Ca(2+) influx at the plasma membrane or function elsewhere within the muscle cell.

Main Methods:

  • Overexpression of TRPC1-yellow fluorescent protein (YFP) in adult mouse muscle fibers.
  • Immunostaining for endogenous TRPC1 and TRPC1-YFP.
  • Measurement of resting electric properties, action potentials, and divalent cation influx.
  • Assessment of contracture response to cyclopiazonic acid (SR Ca(2+) pump blocker).
  • Intracellular Ca(2+) measurements and analysis of Ca(2+) transients.

Main Results:

  • TRPC1 exhibited a striated expression pattern consistent with sarcoplasmic reticulum (SR) localization, not the plasma membrane.
  • TRPC1 overexpression did not alter resting electric properties or resting cation influx.
  • TRPC1-overexpressing fibers showed enhanced contracture upon SR Ca(2+) depletion, independent of external Ca(2+).
  • Intracellular Ca(2+) levels and the rate of Ca(2+) increase during SR Ca(2+) depletion were higher in TRPC1-positive regions.
  • Ca(2+) transients decayed more slowly in TRPC1-YFP-positive cells, indicating altered SR Ca(2+) handling.

Conclusions:

  • TRPC1 channels function as sarcoplasmic reticulum (SR) Ca(2+) leak channels in skeletal muscle.
  • Contrary to previous hypotheses, TRPC1 does not appear to mediate significant sarcolemmal Ca(2+) influx in this context.
  • These findings reveal a novel role for TRPC1 in regulating SR Ca(2+) release and muscle contractility.

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