Functional Compartmentalization of ATP Is Involved in Angiotensin II–Mediated Closure of Cardiac ATP-Sensitive K
            <sup>+</sup>
            Channels

Tsuchiya, Kunihiko; Horie, Minoru; Watanuki, Masato; Albrecht, Carlos A.; Obayashi, Kazuhiko; Fujiwara, Hisayoshi; Sasayama, Shígetake

doi:10.1161/01.cir.96.9.3129

Cited by 21 publications

(19 citation statements)

References 41 publications

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“…7 In fact, raising extracellular ATP from 0 to 1 mmol/L reversibly closed the channel ( Figure 5B). As in the experiments with cromakalim, digoxin 1 mol/L was without effect on the channel activity thus obtained.…”

Section: Inside-out and Open Cell-attached Experimentsmentioning

confidence: 89%

“…7 The inside-out mode was achieved by excising the patch membrane into ATP-free bath solution. Patch pipettes were prepared by pulling borosilicate glass capillaries (Hilgenberg) at 2 to 3 M⍀ for wholecell and at 5 to 7.5 M⍀ for single-channel recordings when filled with pipette solution.…”

Section: Single-cell Preparation and Electrophysiologymentioning

confidence: 99%

“…Streptolysin O was dissolved in the bathing solution at a final concentration of 0.08 U/mL immediately before every experiment and was used within 3 to 4 hours after preparation. 7 All experiments were carried out at Ϸ36°C.…”

Section: Drugsmentioning

confidence: 99%

“…[2][3][4] We have demonstrated in rabbit hearts that the prevention of ischemia-induced reduction of Na ϩ ,K ϩ -ATPase activity during the early phase of sustained ischemia contributes to the infarct size (IS)-limiting effect of IPC because pretreatment with digoxin, an inhibitor of Na ϩ ,K ϩ -ATPase, abolished the cardioprotective effect of IPC. 5 In guinea pig cardiac myocytes, 2 other cardiac glycosides, strophanthidin 6 and ouabain, 7 suppress the opening of K ATP channels by minimizing the consumption of subsarcolemmal ATP by Na ϩ ,K ϩ -ATPase. This notion led us to the hypothesis that the IS-limiting effect of IPC and the inhibitory action of digoxin reflect a functional interaction between Na ϩ ,K ϩ -ATPase and K ATP channels through the ATP concentration ([ATP]) in the subsarcolemmal compartment.…”

mentioning

confidence: 99%

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Coordinate Interaction Between ATP-Sensitive K ⁺ Channel and Na ⁺ ,K ⁺ -ATPase Modulates Ischemic Preconditioning

et al. 1998

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Background-We reported that digoxin abolishes the infarct size (IS)-limiting effect of ischemic preconditioning (IPC).Because ATP-sensitive K ϩ (K ATP ) channels are involved in IPC, we studied whether Na ϩ ,K ϩ -ATPase and K ATP channels functionally interact, thereby modulating IPC. Methods and Results-Rabbits received 30 minutes of coronary artery occlusion followed by 3 hours of reperfusion. IPC was elicited by 5 minutes of occlusion followed by 10 minutes of reperfusion. The IS, expressed as a percentage of the area at risk, was 40.2Ϯ2.8% in control and 39.8Ϯ5.0% in digoxin pretreatment rabbits. Both IPC and pretreatment with cromakalim, a K ATP channel opener, reduced IS to 11.8Ϯ1.8% and 13.4Ϯ2.6% (PϽ0.05 versus control). Digoxin abolished the reduction in IS induced by IPC (33.5Ϯ3.3%), whereas it did not change that induced by cromakalim (18.8Ϯ3.0%). In patch-clamp experiments, digoxin was found to inhibit the opening of K ATP channels in single ventricular myocytes in which ATP depletion had been induced by metabolic stress. In contrast, digoxin had little effect on the channel opening induced by cromakalim. Moreover, the inhibitory action of digoxin on channel activities was dependent on subsarcolemmal ATP concentration. Conclusions-The IS-limiting effect of IPC is modulated by an interaction between K ATP channels and Na ϩ ,K ϩ -ATPase through subsarcolemmal ATP. (Circulation. 1998;98:2905-2910.)

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Section: Inside-out and Open Cell-attached Experimentsmentioning

confidence: 89%

Section: Single-cell Preparation and Electrophysiologymentioning

confidence: 99%

Section: Drugsmentioning

confidence: 99%

mentioning

confidence: 99%

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Coordinate Interaction Between ATP-Sensitive K ⁺ Channel and Na ⁺ ,K ⁺ -ATPase Modulates Ischemic Preconditioning

et al. 1998

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“…In other tissues such as the heart, the physiological relevance of this finding is not entirely clear. There is evidence to suggest that functional compartmentalization of ATP may be involved in receptor signaling, for example, the angiotensin II-mediated closure of cardiac K ATP channels (44). There is also a curious functional interaction between K ATP channels and the Na ϩ /K ϩ pump, whereby the activity of one determines the activity of the other, most likely by competition for the same glycolytically derived ATP (45)(46)(47)(48)(49).…”

Section: Discussionmentioning

confidence: 99%

The Glycolytic Enzymes, Glyceraldehyde-3-phosphate Dehydrogenase, Triose-phosphate Isomerase, and Pyruvate Kinase Are Components of the KATP Channel Macromolecular Complex and Regulate Its Function

Dhar-Chowdhury

Harrell

Han

et al. 2005

Journal of Biological Chemistry

117

111

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The regulation of ATP-sensitive potassium (K ATP ) channel activity is complex and a multitude of factors determine their open probability. Physiologically and pathophysiologically, the most important of these are intracellular nucleotides, with a long-recognized role for glycolytically derived ATP in regulating channel activity. To identify novel regulatory subunits of the K ATP channel complex, we performed a two-hybrid protein-protein interaction screen, using as bait the mouse Kir6.2 C terminus. Screening a rat heart cDNA library, we identified two potential interacting proteins to be the glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and triose-phosphate isomerase. The veracity of interaction was verified by co-immunoprecipitation techniques in transfected mammalian cells. We additionally demonstrated that pyruvate kinase also interacts with Kir6.2 subunits. The physiological relevance of these interactions is illustrated by the demonstration that native Kir6.2 protein similarly interact with GAPDH and pyruvate kinase in rat heart membrane fractions and that Kir6.2 protein co-localize with these glycolytic enzymes in rat ventricular myocytes. The functional relevance of our findings is demonstrated by the ability of GAPDH or pyruvate kinase substrates to directly block the K ATP channel under patch clamp recording conditions. Taken together, our data provide direct evidence for the concept that key enzymes involved in glycolytic ATP production are part of a multisubunit K ATP channel protein complex. Our data are consistent with the concept that the activity of these enzymes (possibly by ATP formation in the immediate intracellular microenvironment of this macromolecular K ATP channel complex) causes channel closure.K ATP channels act as metabolic sensors of a large diversity of cell types by directly coupling their energy metabolism to cellular excitability. This function serves as a crucial regulatory mechanism in the responses of various cell types to their metabolic demand. For example, K ATP channels mediate insulin release from pancreatic ␤ cells, control the firing rate of glucose-responsive neurons in the ventromedial hypothalamus, and protect neurons during hypoxia. K ATP channels also have unique roles in the cardiovascular system. In the coronary vasculature, they participate in the maintenance of the coronary vascular tone, whereas in cardiac myocytes, K ATP channel modulation causes alterations in action potential duration and induction of arrhythmias during cardiac ischemia (1).The minimum requirement for the formation of a heterologously expressed K ATP channel appears to be the presence of two types of subunits, namely a pore-forming subunit (Kir6.x) belonging to the family of inward rectifying K ϩ channel subunits and a sulfonylurea receptor regulatory subunit, which is a member of the family of ABC-cassette proteins (2). However, ion channels are increasingly realized to be multisubunit macromolecular complexes (3-5). Recent evidence suggest that the K ATP channel pro...

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Arrhythmia Mechanisms in Ischemia and Infarction

Coronel¹,

Dun

Boyden

et al. 2009

Novel Therapeutic Targets for Antiarrhythmic Drugs

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Functional Compartmentalization of ATP Is Involved in Angiotensin II–Mediated Closure of Cardiac ATP-Sensitive K ⁺ Channels

Abstract: The inhibitory actions of Ang II on K(ATP) appear to be mediated by an increase in the subsarcolemmal ATP concentration that results from the inhibition of adenylate cyclase activities via AT1 receptors/PTX-sensitive G proteins.

Cited by 21 publications

References 41 publications

Coordinate Interaction Between ATP-Sensitive K ⁺ Channel and Na ⁺ ,K ⁺ -ATPase Modulates Ischemic Preconditioning

Coordinate Interaction Between ATP-Sensitive K ⁺ Channel and Na ⁺ ,K ⁺ -ATPase Modulates Ischemic Preconditioning

The Glycolytic Enzymes, Glyceraldehyde-3-phosphate Dehydrogenase, Triose-phosphate Isomerase, and Pyruvate Kinase Are Components of the KATP Channel Macromolecular Complex and Regulate Its Function

Arrhythmia Mechanisms in Ischemia and Infarction

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Functional Compartmentalization of ATP Is Involved in Angiotensin II–Mediated Closure of Cardiac ATP-Sensitive K + Channels

Abstract: The inhibitory actions of Ang II on K(ATP) appear to be mediated by an increase in the subsarcolemmal ATP concentration that results from the inhibition of adenylate cyclase activities via AT1 receptors/PTX-sensitive G proteins.

Cited by 21 publications

References 41 publications

Coordinate Interaction Between ATP-Sensitive K + Channel and Na + ,K + -ATPase Modulates Ischemic Preconditioning

Coordinate Interaction Between ATP-Sensitive K + Channel and Na + ,K + -ATPase Modulates Ischemic Preconditioning

The Glycolytic Enzymes, Glyceraldehyde-3-phosphate Dehydrogenase, Triose-phosphate Isomerase, and Pyruvate Kinase Are Components of the KATP Channel Macromolecular Complex and Regulate Its Function

Arrhythmia Mechanisms in Ischemia and Infarction

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Resources

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Functional Compartmentalization of ATP Is Involved in Angiotensin II–Mediated Closure of Cardiac ATP-Sensitive K ⁺ Channels

Coordinate Interaction Between ATP-Sensitive K ⁺ Channel and Na ⁺ ,K ⁺ -ATPase Modulates Ischemic Preconditioning

Coordinate Interaction Between ATP-Sensitive K ⁺ Channel and Na ⁺ ,K ⁺ -ATPase Modulates Ischemic Preconditioning