The Na+/Ca2+ exchange blocker SEA0400 fails to enhance cytosolic Ca2+ transient and contractility in canine ventricular cardiomyocytes

被引：24

作者：

Birinyi, Peter ^{[1
]}

Toth, Andras ^{[2
]}

Jona, Istvan ^{[1
]}

Acsai, Karoly ^{[3
]}

Almassy, Janos ^{[1
]}

Nagy, Norbert ^{[2
]}

Prorok, Janos ^{[2
]}

Gherasim, Iuliana ^{[1
]}

Papp, Zoltan ^{[4
]}

Hertelendi, Zita ^{[4
]}

Szentandrassy, Norbert ^{[1
]}

Banyasz, Tamas ^{[1
]}

Fueloep, Ferenc ^{[5
]}

Papp, Julius Gy. ^{[2
,3
]}

Varro, Andras ^{[2
,3
]}

Nanasi, Peter P. ^{[1
]}

Magyar, Janos ^{[1
]}

机构：

[1] Univ Debrecen, Dept Physiol, H-4012 Debrecen, Hungary

[2] Univ Szeged, Dept Pharmacol & Pharmacotherapy, H-6701 Szeged, Hungary

[3] Hungarian Acad Sci, Div Cardiovasc Pharmacol, H-6701 Szeged, Hungary

[4] Univ Debrecen, Dept Cardiol, H-4012 Debrecen, Hungary

[5] Univ Szeged, Inst Pharmaceut Chem, H-6701 Szeged, Hungary

来源：

CARDIOVASCULAR RESEARCH | 2008年 / 78卷 / 03期

关键词：

Na+/Ca2+ exchanger; calcium handling; NCX inhibitors; SEA0400; dog ventricular myocytes;

D O I：

10.1093/cvr/cvn031

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aims This study was designed to evaluate the effects of the Na+/Ca2+ exchange (NCX) inhibitor SEA0400 on Ca2+ handling in isolated canine ventricular myocytes. Methods and results Intracellular Ca2+ ([Ca2+](i)) transients, induced by either field stimulation or caffeine flush, were monitored using Ca2+ indicator dyes. [Ca2+](i)-dependent modulation of the inhibitory effect of SEA0400 on NCX was characterized by the changes in Ni2+-sensitive current in voltage-clamped myocytes. Sarcoplasmic reticulum (SR) Ca2+ release and uptake were studied in SIR membrane vesicles. Gating properties of single-ryanodine receptors were analysed in lipid bilayers. Ca2+ sensitivity of the contractile machinery was evaluated in chemically skinned myocytes. In myocytes paced at 1 Hz, neither diastolic [Ca2+](i) nor the amplitude of [Ca2+](i) transients was significantly altered by SEA0400 up to the concentration of 1 mu M, which was shown to inhibit the exchange current. The blocking effect of SEA0400 on NCX decreased with increasing [Ca2+](i), and it was more pronounced in reverse than in forward mode operation at every [Ca2+](i) examined. The rate of decay of the caffeine-induced [Ca2+](i) transients was decreased significantly by 1 mu M SEA0400; however, this effect was only a fraction of that observed with 10 mM NiCl2. Neither SR Ca2+ release and uptake nor cell shortening and Ca2+ sensitivity of the contractile proteins were influenced by SEA0400. Conclusion The lack of any major SEA0400-induced shift in Ca2+ transients or contractility of myocytes can well be explained by its limited inhibitory effect on NCX (further attenuated by elevated [Ca2+](i) levels) and a concomitant reduction in Ca2+ influx due to the predominantly reverse mode blockade of NCX and suppression of L-type Ca2+ current.

引用

页码：476 / 484

页数：9

共 26 条

[1] Effect of partial blockade of the Na+/Ca2+-exchanger on Ca2+ handling in isolated rat ventricular inyocytes [J].