Pharmacological profiling of store-operated Ca2+ entry in retinal arteriolar smooth muscle

Microcirculation : the Official Journal of the Microcirculatory Society, Inc
Mary K McGahonCharles N Scholfield

Abstract

Pharmacological profiling of SOCE and molecular profiling of ORAI and TRPC expression in arterioles. 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. 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. 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...Continue Reading

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Citations

Jan 6, 2021·Pflügers Archiv : European journal of physiology·Satadru K LahiriXander H T Wehrens
Jun 15, 2021·Frontiers in Pharmacology·Xiaojing LiangWeidong Han

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