Korean J Physiol Pharmacol.  2011 Aug;15(4):189-194. 10.4196/kjpp.2011.15.4.189.

Increased Expression of ATP-sensitive K+ Channels Improves the Right Ventricular Tolerance to Hypoxia in Rabbit Hearts

• Choi SW
• Ahn JS
• Kim HK
• Kim N
• Choi TH
• Park SW
• Ko EA
• Park WS
• Song DK
• Han J

• KMID: 1448923
• DOI: http://doi.org/10.4196/kjpp.2011.15.4.189

Abstract

ATP-sensitive K+ channels (KATP) are major component of preventing ischemia-reperfusion injury. However, there is little information regarding to the expressional difference of K(ATP) and its function between left and right ventricles. In this study, we measured the lactate dehydrogenase release of rabbit heart slices in vitro and determined the difference of the K(ATP) expression at the both ventricles by measuring the level of K(ATP)-forming Kir6.2 (OcKir6.2) mRNA using in situ hybridization. The hearts were preconditioned with 15 min hypoxia and reoxygenated for 15 min before a hypoxic period of 60 min, followed by reoxygenation for 180 min. With hypoxic preconditioning (100% N2) with 15 min, left ventricles (LV) showed higher release of LDH comparing with right ventricles (RV). Adding KATP blocker glibenclamide (10 microM) prior to a hypoxic period of 60 min, hypoxic preconditioning effect of RV was more abolished than LV. With in situ hybridization, the optical density of OcKir6.2 was higher in RV. Therefore, we suggest that different K(ATP) expression between LV and RV is responsible for the different response to hypoxia and hypoxic preconditioning of rabbit hearts.

Keyword

ATP-sensitive K+ channels; Kir6.2; Right ventricle; Hypoxia

MeSH Terms

Anoxia
Glyburide
Heart
Heart Ventricles
In Situ Hybridization
L-Lactate Dehydrogenase
Reperfusion Injury
RNA, Messenger
Glyburide
L-Lactate Dehydrogenase
RNA, Messenger

Figure

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  Fig. 1. mRNA expression of OcKir6.2 in rabbit ventricles. (A) The level of OcKir6.2 expression detected by in situ hybridization was greater in the right ventricle (b) than that in the left ventricle (a). (B) The optical density calculated using ImageJ software was higher in the right than the left ventricle (0.78 vs. 10.5, respectively, n=6, ∗p<0.05).

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  Fig. 2. Whole-cell KATP channel activity was recorded via ramp pulse (from –120 mV to +60 mV, 0.5 dV/dt) from right and left ventricular myocytes. Representative currents (A) and I-V relationship (B) from right and left myocytes. Application of pinacidil activated KATP channels. (C) Current density at 0 mV was bigger in right than left myocytes (104.7 and 76.3 pA/pF, respectively, n=7, ∗p<0.05).

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  Fig. 3. LDH release in the left and right ventricles under conditions of hypoxia and hypoxic preconditioning. (A) Measurement of LDH release under hypoxic conditions from 1 to 5 h. LDH release in the left ventricle was higher than that in the right ventricle (58.2% vs. 49.1%, respectively, n=6; ∗p<0.05). (B) Measurement of LDH release in hypoxia after hypoxic preconditioning from 1 to 5 h. Left ventricle LDH release was higher than that in the right ventricle (27.3% and 20%, respectively, n=6; ∗p<0.05). LV (left ventricle, ❍), RV (right ventricle, ), PC, hypoxic preconditioning.

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  Fig. 4. LDH release in response to glibenclamide treatment in each ventricle. Differences in LDH release between PC () and PC+ glibenclamide (Δ) were greater in the right ventricle (B) than in the left ventricle (A) (n=6, ∗p<0.05). (C) Glibenclamide sensitivity in the left and right ventricles. LDH release from the left ventricle was greater under PC conditions. However, with addition of glibenclamide, LDH release was not significantly different between the left and right ventricles (n=6, ∗p<0.05). PC, hypoxic preconditioning.

Reference

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