title: Pharmacological profiling of store-operated Ca2+ entry in retinal arteriolar smooth muscle.
abstract: OBJECTIVE
  Pharmacological profiling of SOCE and molecular profiling of ORAI and TRPC expression in arterioles.
  
  
  METHODS
  Fura-2-based microfluorimetry was used to assess CPA-induced SOCE in rat retinal arteriolar myocytes. Arteriolar ORAI and TRP transcript expression was screened using RT-PCR.
  
  
  RESULTS
  The SKF96365 and LOE908 blocked SOCE (IC(50) s of 1.2 and 1.4 μm, respectively). Gd(3+) and La(3+) potently inhibited SOCE (IC(50) s of 21 and 42 nm, respectively), but Ni(2+) showed lower potency (IC(50) = 11.6 μm). 2APB inhibited SOCE (IC(50) = 3.7 μm) but enhanced basal influx (>100 μm). Verapamil and nifedipine had no effect at concentrations that inhibit L-type Ca(2+) channels, but diltiazem inhibited SOCE by approximately 40% (≥0.1 μm). The RT-PCR demonstrated transcript expression for ORAI 1, 2, and 3, and TRPC1, 3, 4, and 7. Transcripts for TRPV1 and 2, which are activated by 2APB, were also expressed.
  
  
  CONCLUSIONS
  The pharmacological profile of SOCE in retinal arteriolar smooth muscle appears unique when compared with other vascular tissues. This suggests that the molecular mechanisms underlying SOCE can differ, even in closely related tissues. Taken together, the pharmacological and molecular data are most consistent with involvement of TRPC1 in SOCE, although involvement of ORAI or other TRPC channels cannot be excluded.
authors.affiliation: Centre for Vision and Vascular Science, School of Medicine, Dentistry and Biomedical Sciences, Institute of Clinical Science, The Royal Victoria Hospital, Queen's University Belfast, Belfast, UK.
authors.forename: Mary K
authors.initials: MK
authors.lastname: McGahon
authors.forename: Jonathan
authors.initials: J
authors.lastname: McKee
authors.forename: Durga P
authors.initials: DP
authors.lastname: Dash
authors.forename: Eoin
authors.initials: E
authors.lastname: Brown
authors.forename: David A
authors.initials: DA
authors.lastname: Simpson
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Curtis
authors.forename: James G
authors.initials: JG
authors.lastname: McGeown
authors.forename: Charles N
authors.initials: CN
authors.lastname: Scholfield
mesh_terms: D000818:Animals; D001160:Arterioles / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002118:Calcium