Molecular candidates for capacitative and non-capacitative Ca2+ entry in smooth muscle

Novartis Found Symp. 2002:246:81-90; discussion 221-7.

Abstract

Recent investigations have revealed that mammalian homologues of transient receptor potential (TRP) protein (TRP1-7) are promising candidates for Ca2+ entry mechanisms (or channels) associated with various metabotropic G protein-coupled receptors (GPCRs) in smooth muscle, stimulation of which generates lipid second messengers and depletes internal stores. RT-PCR and immunocytochemical experiments have demonstrated that although the level of expression varies depending on tissues, the major TRP isoforms expressed in smooth muscle are TRP4, 6 and 7. In some vascular preparations, the significant expression of TRP1 mRNA and protein is also detected. Consistent with these findings, recent functional studies using TRP6- and TRP1-specific antisense oligonucleotides and antibodies have suggested that TRP6 is the essential component of alpha1-adrenoceptor activated, store depletion-independent Ca2+ entry channels, while TRP1 is partly involved in Ca2+ entry associated with store depletion or capacitative Ca2+ entry. In addition, coexpression of different TRP isoforms results in the appearance of cation channels showing novel properties reminiscent of some native GPCR-activated Ca2+-permeable non-selective cation channels. Thus, at present, TRP proteins may be the most important clues for elucidating the molecular entities of receptor- and store-operated Ca2+ entry mechanisms in smooth muscle and their roles in smooth muscle functions.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium / physiology*
  • Calcium Channels / genetics
  • Calcium Channels / physiology
  • Calcium Signaling / physiology*
  • GTP-Binding Proteins / metabolism
  • Humans
  • Mammals
  • Muscle, Smooth / physiology*
  • Muscle, Smooth, Vascular / physiology
  • Receptors, Cell Surface / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • TRPC Cation Channels

Substances

  • Calcium Channels
  • Receptors, Cell Surface
  • TRPC Cation Channels
  • transient receptor potential cation channel, subfamily C, member 1
  • GTP-Binding Proteins
  • Calcium