title: TRP4 (CCE1) protein is part of native calcium release-activated Ca2+-like channels in adrenal cells.
abstract: Mammalian TRP proteins have been implicated to function as ion channel subunits responsible for agonist-induced Ca(2+) entry. To date, TRP proteins have been extensively studied by heterologous expression giving rise to diverse channel properties and activation mechanisms including store-operated mechanisms. However, the molecular structure and the functional properties of native TRP channels still remain elusive. Here we analyze the properties of TRP4 (CCE1) channels in their native environment and characterize TRP expression patterns and store-operated calcium currents that are endogenous to bovine adrenal cells. We show by Northern blot analysis, immunoblots, and immunohistochemistry that TRP4 transcripts and TRP4 protein are present in the adrenal cortex but absent in the medulla. Correspondingly, bovine adrenal cortex cells express TRP4 abundantly. The only other TRP transcript found at considerable levels was TRP1, whereas TRP2, TRP3, TRP5(CCE2), and TRP6 were not detectable. Depletion of calcium stores with inositol 1,4,5-trisphosphate or thapsigargin activates store-operated ion channels in adrenal cells. These channels closely resemble calcium release-activated Ca(2+) (CRAC) channels. Expression of trp4(CCE1) cDNA in antisense orientation significantly reduces both, the endogenous CRAC-like currents and the amount of native TRP4 protein. These results demonstrate that TRP4 contributes essentially to the formation of native CRAC-like channels in adrenal cells.
authors.affiliation: Institut für Pharmakologie und Toxikologie, Institut für Anatomie, Institut für Medizinische Biochemie, und Institut für Physiologie, Universität des Saarlandes, D-66421 Homburg, Germany. stephan.philipp@med-rz.uni-sb.de
authors.forename: S
authors.initials: S
authors.lastname: Philipp
authors.forename: C
authors.initials: C
authors.lastname: Trost
authors.forename: J
authors.initials: J
authors.lastname: Warnat
authors.forename: J
authors.initials: J
authors.lastname: Rautmann
authors.forename: N
authors.initials: N
authors.lastname: Himmerkus
authors.forename: G
authors.initials: G
authors.lastname: Schroth
authors.forename: O
authors.initials: O
authors.lastname: Kretz
authors.forename: W
authors.initials: W
authors.lastname: Nastainczyk
authors.forename: A
authors.initials: A
authors.lastname: Cavalie
authors.forename: M
authors.initials: M
authors.lastname: Hoth
authors.forename: V
authors.initials: V
authors.lastname: Flockerzi
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins; D002417:Cattle; D016373:DNA, Antisense / Q000494:pharmacology; D004553:Electric Conductivity; D017403:In Situ Hybridization; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000302:isolation & purification; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D050052:TRPC Cation Channels; D019284:Thapsigargin / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D015220:Calcium Channels; D027682:Cation Transport Proteins; D016373:DNA, Antisense; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C489571:TRPC4 ion channel; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium