Molecular candidates for capacitative and non-capacitative Ca2+ entry in smooth muscle.
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.
Inoue
Ryuji
R
Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Mori
Yasuo
Y
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D008322:Mammals; D009130:Muscle, Smooth / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050052:TRPC Cation Channels
D015220:Calcium Channels; D011956:Receptors, Cell Surface; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D019204:GTP-Binding Proteins; D002118:Calcium