Discrimination of intracellular calcium store subcompartments using TRPV1 (transient receptor potential channel, vanilloid subfamily member 1) release channel activity

Biochem J. 2003 Apr 15;371(Pt 2):341-50. doi: 10.1042/BJ20021381.


The store-operated calcium-release-activated calcium current, I (CRAC), is a major mechanism for calcium entry into non-excitable cells. I (CRAC) refills calcium stores and permits sustained calcium signalling. The relationship between inositol 1,4,5-trisphosphate receptor (InsP(3)R)-containing stores and I (CRAC) is not understood. A model of global InsP(3)R store depletion coupling with I (CRAC) activation may be simplistic, since intracellular stores are heterogeneous in their release and refilling activities. Here we use a ligand-gated calcium channel, TRPV1 (transient receptor potential channel, vanilloid subfamily member 1), as a new tool to probe store heterogeneity and define intracellular calcium compartments in a mast cell line. TRPV1 has activity as an intracellular release channel but does not mediate global calcium store depletion and does not invade a store coupled with I (CRAC). Intracellular TRPV1 localizes to a subset of the InsP(3)R-containing stores. TRPV1 sensitivity functionally subdivides the InsP(3)-sensitive store, as does heterogeneity in the sarcoplasmic/endoplasmic-reticulum Ca(2+)-ATPase isoforms responsible for store refilling. These results provide unequivocal evidence that a specific 'CRAC store' exists within the InsP(3)-releasable calcium stores and describe a novel methodology for manipulation of intracellular free calcium.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / physiology*
  • Calcium Channels / drug effects
  • Calcium Channels / physiology*
  • Capsaicin / pharmacology*
  • Carbachol / pharmacology
  • Cytosol / physiology
  • Genetic Vectors
  • Inositol 1,4,5-Trisphosphate Receptors
  • Leukemia, Basophilic, Acute
  • Models, Biological
  • Nociceptors / drug effects
  • Nociceptors / physiology
  • Rats
  • Receptors, Cytoplasmic and Nuclear / physiology
  • Receptors, Drug / drug effects
  • Receptors, Drug / physiology*
  • Recombinant Proteins / metabolism
  • TRPC Cation Channels
  • TRPV Cation Channels
  • Transfection
  • Tumor Cells, Cultured
  • Vaccinia virus / genetics


  • Calcium Channels
  • Inositol 1,4,5-Trisphosphate Receptors
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Drug
  • Recombinant Proteins
  • TRPC Cation Channels
  • TRPV Cation Channels
  • TRPV1 receptor
  • transient receptor potential cation channel, subfamily C, member 1
  • Carbachol
  • Capsaicin
  • Calcium