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

Seong Woo Choi; Jun Seok Ahn; Hyoung Kyu Kim; Nari Kim; Tae-Hoon Choi; Sung-Woo Park; En A Ko; Won Sun Park; Dae-Kyu Song; Jin Han

doi:10.4196/kjpp.2011.15.4.189

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Choi, Ahn, Kim, Kim, Choi, Park, Ko, Park, Song, and Han: Increased Expression of ATP-sensitive K+ Channels Improves the Right Ventricular Tolerance to Hypoxia in Rabbit Hearts

Original Article

Korean J Physiol Pharmacol 2011;15(4):189-194.

Published online: 18 February 2011

DOI: https://doi.org/10.4196/kjpp.2011.15.4.189

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

Seong Woo Choi^1,^∗, Jun Seok Ahn^1,^∗, Hyoung Kyu Kim¹, Nari Kim¹, Tae-Hoon Choi², Sung-Woo Park³, En A Ko¹, Won Sun Park⁴, Dae-Kyu Song^5,^#, Jin Han^1,^#,

¹National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 614-735, Korea

²Department of Sport and Leisure Studies, Andong Science College, Andong 760-709, Korea

³Department of Neuropsychiatry, College of Medicine, Paik Inje Memorial Clinical Research Institute, Inje University, Busan 614-735, Korea

⁴Department of Physiology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea

⁵Department of Physiology & Chronic Disease Research Center, Keimyung University School of Medicine, Daegu 700-712, Korea

Corresponding to: Jin Han, National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University 633-165, Gaegeum-dong, Busanjin-gu, Busan 613-735, Korea. (Tel) 82-51-890-6727, (Fax) 82-51-894-5714, (E-mail) phyhanj@inje.ac.kr

^∗ Both authors contributed equally to this work.

^# Both authors contributed equally to this work.

Received 13 April 2011 Revised 21 June 2011 Accepted 2 July 2011

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

ATP-sensitive K⁺ channels (K_ATP) 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 K_ATP blocker glibenclamide (10μM) 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.

Keywords: ATP-sensitive K⁺ channels, Kir6.2, Right ventricle, Hypoxia

References

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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).

Fig. 2.

Whole-cell K_ATP 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 K_ATP 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).

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.

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.

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