Transient receptor potential channel activation causes a novel form of [Ca 2+]I oscillations and is not involved in capacitative Ca 2+ entry in glial cells.
Astrocytes express transient receptor potential channels (TRPCs), which have been implicated in Ca 2+ influx triggered by intracellular Ca 2+ stores depletion, a phenomenon known as capacitative Ca 2+ entry. We studied the properties of capacitative Ca 2+ entry in astrocytes by means of single-cell Ca 2+ imaging with the aim of understanding the involvement of TRPCs in this function. We found that, in astrocytes, capacitative Ca 2+ entry is not attributable to TRPC opening because the TRPC-permeable ions Sr2+ and Ba2+ do not enter astrocytes during capacitative Ca 2+ entry. Instead, natively expressed oleyl-acetyl-glycerol (OAG) (a structural analog of DAG) -sensitive TRPCs, when activated, initiate oscillations of cytosolic Ca 2+ concentration ([Ca 2+]i) pharmacologically and molecularly consistent with TRPC3 activation. OAG-induced [Ca 2+]i oscillations are not affected by inhibition of inositol trisphosphate (InsP3) production or blockade of the InsP3 receptor, therefore representing a novel form of [Ca 2+]i signaling. Instead, high [Ca 2+]i inhibited oscillations, by closing the OAG-sensitive channel. Also, treatment of astrocytes with antisense against TRPC3 caused a consistent decrease of the cells responding to OAG. Exogenous OAG but not endogenous DAG seems to activate TRPC3. In conclusion, in glial cells, natively expressed TRPC3s mediates a novel form of Ca 2+ signaling, distinct from capacitative Ca 2+ entry, which suggests a specific signaling function for this channel in glial cells.
Grimaldi
Maurizio
M
Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA. mgrimaldi@usuhs.mil
Maratos
Marina
M
Verma
Ajay
A
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004075:Diglycerides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism; D007150:Immunohistochemistry; D007424:Intracellular Fluid / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D020033:Protein Isoforms / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013324:Strontium / Q000494:pharmacology; D050052:TRPC Cation Channels; D019284:Thapsigargin / Q000494:pharmacology
D015220:Calcium Channels; D004075:Diglycerides; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007473:Ion Channels; D016376:Oligonucleotides, Antisense; D020033:Protein Isoforms; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C096351:transient receptor potential cation channel, subfamily C, member 1; D019284:Thapsigargin; C038237:1-oleoyl-2-acetylglycerol; D000255:Adenosine Triphosphate; D002118:Calcium; D013324:Strontium