Pharmacological profiling of store-operated Ca(2+) entry in retinal arteriolar smooth muscle

Mary K. McGahon, Jonathan McKee, Durga P. Dash, E Brown, David A. Simpson, Timothy M. Curtis, James G. McGeown, Charles N. Scholfield

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Objective: Pharmacological profiling of store-operated Ca(2+) entry (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 were screened using RT-PCR. 
Results: SKF96365 and LOE908 blocked SOCE (IC(50) s of 1.2µM and 1.4µM, respectively). Gd(3+) and La(3+) potently inhibited SOCE (IC(50) s of 21nM and 42nM, respectively), but Ni(2+) showed lower potency (IC(50) = 11.6µM). 2-aminoethyldiphenyl borate (2APB) inhibited SOCE (IC(50) = 3.7µM) but enhanced basal influx (>100µM). Verapamil and nifedipine had no effect at concentrations that inhibit L-type Ca(2+) channels, but diltiazem inhibited SOCE by approximately 40% (=0.1µM). 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. 
Conclusion: The pharmacological profile of SOCE in retinal arteriolar smooth muscle appears unique when compared to 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. © 2012 John Wiley & Sons Ltd.
Original languageEnglish
Pages (from-to)586-597
Number of pages12
JournalMicrocirculation (New York, N.Y. : 1994)
Volume19
Issue number7
Early online date09 Oct 2012
DOIs
Publication statusPublished - Oct 2012

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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