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Pharmacological Profiling of Store‐Operated Ca 2+ Entry in Retinal Arteriolar Smooth Muscle
Author(s) -
MCGAHON MARY K.,
MCKEE JONATHAN,
DASH DURGA P.,
BROWN EOIN,
SIMPSON DAVID A.,
CURTIS TIMOTHY M.,
McGEOWN JAMES G.,
SCHOLFIELD CHARLES N.
Publication year - 2012
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/j.1549-8719.2012.00192.x
Subject(s) - orai1 , chemistry , verapamil , trpc , stim1 , nifedipine , vascular smooth muscle , pharmacology , transient receptor potential channel , endocrinology , endoplasmic reticulum , biochemistry , biology , receptor , calcium , smooth muscle , organic chemistry
Please cite this paper as: McGahon MK, McKee J, Dash DP, Brown E, Simpson DA, Curtis TM, McGeown JG, Scholfield CN. Pharmacological profiling of store‐operated Ca 2+ entry in retinal arteriolar smooth muscle. Microcirculation 19: 586–597, 2012. 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 μ m , respectively). Gd 3+ and La 3+ potently inhibited SOCE (IC 50 s of 21 and 42 n m , respectively), but Ni 2+ showed lower potency (IC 50 = 11.6 μ m ). 2APB inhibited SOCE (IC 50 = 3.7 μ m ) but enhanced basal influx (>100 μ m ). Verapamil and nifedipine had no effect at concentrations that inhibit L‐type Ca 2+ channels, but diltiazem inhibited SOCE by approximately 40% (≥0.1 μ m ). 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.