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

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

doi:10.4196/kjpp.2011.15.4.189

Cited by 7 publications

(6 citation statements)

References 23 publications

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“…In agreement, a number of studies observed larger I Ks and I to in RV compared with LV. [27][28][29][30] In addition, some studies have observed changes in the gene expression of K ir 6.1/K ir 6.2, underlying the ATP-sensitive K + current (I KATP ), 31,32 NCX1 33 and K ir 2.1/K ir 2.3, molecular components of I K1 . 34,35 Consistent with these molecular data, I K1 density is larger in LV myocytes from guinea pigs, contributing to the stabilisation of the high-frequency rotors in LV.…”

Section: Differences In Ion Channel Propertiesmentioning

confidence: 99%

Differences in Left Versus Right Ventricular Electrophysiological Properties in Cardiac Dysfunction and Arrhythmogenesis

Molina

Heijman

Dobrev

2016

Arrhythmia &Amp; Electrophysiology Review

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Optimal cardiac function depends on appropriate rate and force of contraction, with specific cardiac regions having developed particular beat-to-beat properties depending on their individual functions. For example, isovolumetric contraction time is shorter in the right ventricle (RV) than in the left ventricle (LV). At the cellular level, cardiac function is regulated by regional cardiomyocyte electrophysiological and Ca 2+ -handling properties (see Figure 1). Differences in these properties between nodal cells and working myocardium, 1,2 atrial and ventricular cardiomyocytes 1,3,4 and different layers of the LV wall (endo-, mid-and epicardium) [5][6][7] have been well established. Although electrophysiological differences between left and right sides of the heart have been less extensively characterised there is evidence for clinically relevant left-toright differences in the atrium 1,[8][9][10] and the ventricle. 1,5,[11][12][13][14] Here, we review the known differences in LV and RV electrophysiology and Ca 2+ handling at baseline and during pathophysiological conditions. Furthermore, we discuss the implications of these differences for arrhythmogenesis. Basic Cardiac Electrophysiology and Arrhythmia MechanismsCardiac excitation-contraction (EC) coupling is a sequence of events occurring in cardiomyocytes upon electrical activation, resulting in the generation of an action potential (AP) and subsequent cardiomyocyte contraction (see Figure 2). This sequence shows many similarities between different cell types, notably between LV and RV cardiomyocytes.In this section we briefly summarise the common features. Figure 2A). Moreover, the Ca 2+ entering the cardiomyocyte through L-type Ca 2+ channels plays a critical role initiating EC coupling by activating type-2 ryanodine receptor (RyR2) channels on the sarcoplasmic reticulum (SR) membrane, producing a much larger SR Ca 2+ release. This process is termed Ca 2+ -induced Ca 2+ release (CICR) and results in an increase in the cytoplasmic Ca 2+ concentration sufficient to activate the contractile apparatus, initiating cardiomyocyte contraction. 15 Subsequently, resequestration of Ca 2+ in the SR by the SR Ca 2+ ATPase type-2a (SERCA2a) and extrusion of Ca 2+ to the extracellular space by the Na + -Ca 2+ exchanger type-1 (NCX1) returns cytosolic Ca 2+ to diastolic levels, promoting cellular relaxation. Finally, ionic homeostasis of intracellular Na + and K + is maintained by the Na + / Abstract A wide range of ion channels, transporters, signaling pathways and tissue structure at a microscopic and macroscopic scale regulate the electrophysiological activity of the heart. Each region of the heart has optimised these properties based on its specific role during the cardiac cycle, leading to well-established differences in electrophysiology, Ca 2+ handling and tissue structure between atria and ventricles and between different layers of the ventricular wall. Similarly, the right ventricle (RV) and left ventricle (LV) have different embryological, structural, metabol...

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Section: Differences In Ion Channel Propertiesmentioning

confidence: 99%

Differences in Left Versus Right Ventricular Electrophysiological Properties in Cardiac Dysfunction and Arrhythmogenesis

Molina

Heijman

Dobrev

2016

Arrhythmia &Amp; Electrophysiology Review

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“…35 Regional heterogeneity between the LV and the RV may also exist for ATP-activated K + current, I KATP . 36,37 In contrast to these electrophysiological studies, a recent proteomic study reported no difference in the expression level of >600 proteins between the RV and the LV from pig and rabbit. Most of these were contractile/structural proteins, oxidative phosphorylation components, and enzymes from intermediary metabolism.…”

mentioning

confidence: 92%

“…In this species, a larger RV I Ks correlates with a higher expression of KCNQ1 and KCNE1, the principal and auxiliary subunit of the I Ks channel, respectively . Regional heterogeneity between the LV and the RV may also exist for ATP‐activated K + current, I KATP …”

Section: Introductionmentioning

confidence: 98%

Interventricular Differences in β‐Adrenergic Responses in the Canine Heart: Role of Phosphodiesterases

Molina

Johnson

Mehel

et al. 2014

JAHA

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BackgroundRV and LV have different embryologic, structural, metabolic, and electrophysiologic characteristics, but whether interventricular differences exist in β‐adrenergic (β‐AR) responsiveness is unknown. In this study, we examine whether β‐AR response and signaling differ in right (RV) versus left (LV) ventricles.Methods and ResultsSarcomere shortening, Ca2+ transients, ICa,L and IKs currents were recorded in isolated dog LV and RV midmyocytes. Intracellular [cAMP] and PKA activity were measured by live cell imaging using FRET‐based sensors. Isoproterenol increased sarcomere shortening ≈10‐fold and Ca2+‐transient amplitude ≈2‐fold in LV midmyocytes (LVMs) versus ≈25‐fold and ≈3‐fold in RVMs. FRET imaging using targeted Epac2camps sensors revealed no change in subsarcolemmal [cAMP], but a 2‐fold higher β‐AR stimulation of cytoplasmic [cAMP] in RVMs versus LVMs. Accordingly, β‐AR regulation of ICa,L and IKs were similar between LVMs and RVMs, whereas cytoplasmic PKA activity was increased in RVMs. Both PDE3 and PDE4 contributed to the β‐AR regulation of cytoplasmic [cAMP], and the difference between LVMs and RVMs was abolished by PDE3 inhibition and attenuated by PDE4 inhibition. Finally LV and RV intracavitary pressures were recorded in anesthetized beagle dogs. A bolus injection of isoproterenol increased RV dP/dtmax≈5‐fold versus 3‐fold in LV.ConclusionCanine RV and LV differ in their β‐AR response due to intrinsic differences in myocyte β‐AR downstream signaling. Enhanced β‐AR responsiveness of the RV results from higher cAMP elevation in the cytoplasm, due to a decreased degradation by PDE3 and PDE4 in the RV compared to the LV.

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“…Single-channel currents were sampled at 5 kHz and filtered at 2 kHz using an analog-digital interface (Digidata 1440A, Molecular Devices, USA). Voltage pulse was modified from the ramp protocol used by Choi et al [18]. Experiments were performed at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Acute Hypoxia Activates an ENaC-like Channel in Rat Pheochromocytoma (PC12) Cells

Bae

Yoo

Park

et al. 2013

Korean J Physiol Pharmacol

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Cells can resist and even recover from stress induced by acute hypoxia, whereas chronic hypoxia often leads to irreversible damage and eventually death. Although little is known about the response(s) to acute hypoxia in neuronal cells, alterations in ion channel activity could be preferential. This study aimed to elucidate which channel type is involved in the response to acute hypoxia in rat pheochromocytomal (PC12) cells as a neuronal cell model. Using perfusing solution saturated with 95% N2 and 5% CO2, induction of cell hypoxia was confirmed based on increased intracellular Ca2+ with diminished oxygen content in the perfusate. During acute hypoxia, one channel type with a conductance of about 30 pS (2.5 pA at -80 mV) was activated within the first 2~3 min following onset of hypoxia and was long-lived for more than 300 ms with high open probability (Po, up to 0.8). This channel was permeable to Na+ ions, but not to K+, Ca+, and Cl- ions, and was sensitively blocked by amiloride (200 nM). These characteristics and behaviors were quite similar to those of epithelial sodium channel (ENaC). RT-PCR and Western blot analyses confirmed that ENaC channel was endogenously expressed in PC12 cells. Taken together, a 30-pS ENaC-like channel was activated in response to acute hypoxia in PC12 cells. This is the first evidence of an acute hypoxia-activated Na+ channel that can contribute to depolarization of the cell.

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

Cited by 7 publications

References 23 publications

Differences in Left Versus Right Ventricular Electrophysiological Properties in Cardiac Dysfunction and Arrhythmogenesis

Differences in Left Versus Right Ventricular Electrophysiological Properties in Cardiac Dysfunction and Arrhythmogenesis

Interventricular Differences in β‐Adrenergic Responses in the Canine Heart: Role of Phosphodiesterases

Acute Hypoxia Activates an ENaC-like Channel in Rat Pheochromocytoma (PC12) Cells

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