SEA0400, a novel Na+/Ca2+ exchanger inhibitor, reduces calcium overload induced by ischemia and reperfusion in mouse ventricular myocytes

Title:

SEA0400, a novel Na+/Ca2+ exchanger inhibitor, reduces calcium overload induced by ischemia and reperfusion in mouse ventricular myocytes

Creator:

Wang, J., Zhang, Z., Yuehua Hu, Hou, X., Cui, Q., Zang, Y., and Wang, Chen

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:a383484f-0bfe-4e22-9146-002f929142b8
uuid:a383484f-0bfe-4e22-9146-002f929142b8
issn:0862-8408

Subject:

Fyziologie člověka a srovnávací fyziologie, fyziologie, ischemie, human physiology, ischemia, SEA0400, patch clamp, Na+/Ca2+ exchanger current, 14, and 612

Type:

article, články, model:article, and TEXT

Format:

print, bez média, and svazek

Description:

Given the potential clinical benefit of inhibiting Na+/Ca2+ exchanger (NCX) activity dur ing myocardial ischemia reperfusion (I/R), pharmacological approaches have been pursued to both inhibit and clarify the importance of this exchanger. SEA0400 was reported to have a potent NCX selectivity. Thus, we examined the effect of SEA0400 on NCX currents and I/R induced intracellular Ca2+ overload in mouse ventricular myocytes using patch clamp techniques and fluorescence measurements. Ischemia significantly inhibited inward and outward NCX current (from -0.04±0.01nA to 0 nA at -100 mV; from 0.23±0.08 nA to 0.11±0.03 nA at +50 mV, n=7). Subsequent reperfusion not only restored the current rapidly but enhanced the current amplitude obviously, especially the outward currents (from 0.23±0.08 nA to 0.49±0.12 nA at +50 mV, n=7). [Ca2+]i, expressed as the ratio of Fura-2 fluorescence intensity, increased to 138±7 % (P<0.01) during ischemia and to 210±11 % (P<0.01) after reperfusion. The change of NCX current and the increase of [Ca 2+]i during I/R can be blocked by SEA0400 in a dose-dependent manner with an EC50 value of 31 nM and 28 nM for the inward and outward NCX current, respectively. The results suggested that SEA0400 is a potent NCX inhibitor, which can protect mouse cardiac myocytes from Ca2+ overload during I/R injuries., J. Wang, Z. Zhang, Y. Hu, X. Hou, Q. Cui, Y. Zang, C. Wang., and Obsahuje bibliografii a bibliografické odkazy

Language:

English

Rights:

http://creativecommons.org/licenses/by-nc-sa/4.0/
policy:public

Source:

Physiological research | 2007 Volume:56 | Number:1

Harvested from:

CDK

Metadata only:

false