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2‐aminoethoxydiphenyl borate (2‐APB) and gentamicin inhibit thromboxane A 2 induced calcium responses in cardiac myocytes
Author(s) -
Kosloski Lisa M.,
Gilbert William J. R.,
Orr James A.,
Moore David S.,
Wacker Michael J.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.751.10
Subject(s) - calcium , myocyte , chemistry , calcium in biology , intracellular , endocrinology , medicine , thromboxane , pharmacology , biophysics , biology , biochemistry , platelet
Previous work in our laboratory has shown that accelerated idioventricular arrhythmias are induced by the administration of a thromboxane A 2 (TxA 2 ) mimetic, U46619 (U4), into the left atrium of the anesthetized rabbit. Preliminary experiments indicate that application of U4 to cultured myocytes increases intracellular calcium. Therefore, we hypothesize that TxA 2 may produce arrhythmias by directly stimulating cardiac myocytes and altering intracellular calcium via activation of the IP 3 pathway. Ventricular cardiac myocytes from the rabbit heart were isolated and treated with the fluorescent indicator fluo‐4 in 3 series of experiments to examine the effects of U4 and 2 inhibitors of IP 3 mediated calcium release, 2‐APB and gentamicin. In series 1, 5 μM U4 was added to cells that had not been pretreated resulting in an average increase in calcium of 33.7 ± 65.7% (n = 24). In series 2, cells that were pretreated with 1.5 μM 2‐APB exhibited an average calcium increase of 8.1 ± 11.7% upon addition of U4 (p = 0.07; n = 15). In series 3, cells that were pretreated with 1.5 μM gentamicin exhibited an average calcium increase of 6.4 ± 8.5% after addition of U4 (p = 0.03; n = 21). In all 3 series, KCl (50 μM) was administered after U4 as a positive control; cells that did not respond to KCl were discarded from further analysis. These data support the hypothesis that TxA 2 induces a calcium response in cardiac myocytes that involves the IP 3 pathway.