Role of the Sarcolemmal Adenosine Triphosphate–Sensitive Potassium Channel in Hyperkalemic Cardioplegia-Induced Myocyte Swelling and Reduced Contractility

Prasad, Sandip M.; Al-Dadah, Ashraf; Byrd, Gregory D.; Flagg, Thomas P.; Gomes, Jefferson; Damiano, Ralph J.; Nichols, Colin G.; Lawton, Jennifer S.

doi:10.1016/j.athoracsur.2005.06.055

Cited by 20 publications

(53 citation statements)

References 24 publications

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“…These data indicate no role of Kir6.1 in detrimental swelling secondary to the stress of cardioplegia (as was found with Kir6.2), and that cardioprotection by diazoxide remains intact in the absence of Kir6.1. Similar to our previous findings with deletion of Kir6.2 myocytes, Kir6.1 knockout myocytes in the present study did not exhibit a reduction in myocyte contractility during stress (9). Despite the detrimental volume change observed in Kir6.1(−/−) myocytes exposed to stress, there was no subsequent decline in contractility.…”

Section: Discussionsupporting

confidence: 90%

“…The adenosine triphosphate-sensitive K ATP channel opener diazoxide provides volume homeostasis and preserves contractility in isolated myocytes of mice, rabbits, and humans in response to stress (exposure to hyperkalemic cardioplegia, metabolic inhibition, or hyposmotic stress) (7,9,11,22). The mechanism of cardioprotection by diazoxide could be at a mitochondrial K ATP channel location or via a K ATP channel-independent location.…”

Section: Discussionmentioning

confidence: 99%

“…Pharmacologic opening of K ATP channels provides cardioprotection and mimics ischemic preconditioning in multiple animal models (3)(4)(5)(6)(7)(8)(9)(10) and in human myocytes (11). Paradoxically, the cell surface (sarcolemmal) K ATP channel (sK ATP ) has been implicated in myocyte swelling secondary to stress, and deletion of the sK ATP channel subunit Kir6.2 provides resistance to myocyte swelling secondary to stress (9,12).…”

Section: Introductionmentioning

confidence: 99%

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Diazoxide Cardioprotection Is Independent of Adenosine Triphosphate-Sensitive Potassium Channel Kir 6.1 Subunit in Response to Stress

Janjua

Zhang

Henn

et al. 2014

Journal of the American College of Surgeons

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Background-The sarcolemmal adenosine triphosphate-sensitive potassium channel (sK ATP ), composed primarily of Kir6.2 and SUR2A subunits, has been implicated in cardiac myocyte volume regulation during stress; however, it is not involved in cardioprotection by the K ATP channel opener diazoxide. Paradoxically, the sK ATP channel subunit Kir6.2 is necessary for detrimental myocyte swelling secondary to stress. The Kir6.1 subunit may also contribute to K ATP channels in the heart, and we hypothesized that this subunit may play a role in myocyte volume regulation in response to stress.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Diazoxide Cardioprotection Is Independent of Adenosine Triphosphate-Sensitive Potassium Channel Kir 6.1 Subunit in Response to Stress

Janjua

Zhang

Henn

et al. 2014

Journal of the American College of Surgeons

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“…The adenosine triphosphate–sensitive K ATP channel opener diazoxide provides volume homeostasis and preserves contractility in isolated myocytes of mice, rabbits, and humans in response to stress (exposure to hyperkalemic cardioplegia, metabolic inhibition, or hyposmotic stress) (7, 9, 11, 22). The mechanism of cardioprotection by diazoxide could be at a mitochondrial K ATP channel location or via a K ATP channel-independent location.…”

Section: Discussionmentioning

confidence: 99%

“…Pharmacologic opening of K ATP channels provides cardioprotection and mimics ischemic preconditioning in multiple animal models (3–10) and in human myocytes (11). Paradoxically, the cell surface (sarcolemmal) K ATP channel (sK ATP ) has been implicated in myocyte swelling secondary to stress, and deletion of the sK ATP channel subunit Kir6.2 provides resistance to myocyte swelling secondary to stress (9, 12). …”

Section: Introductionmentioning

confidence: 99%

Diazoxide Cardioprotection Is Independent of Adenosine Triphosphate-Sensitive Potassium Channel Kir6.1 Subunit in Response to Stress

Henn

Janjua

Zhang

et al. 2015

Journal of the American College of Surgeons

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Background The sarcolemmal adenosine triphosphate-sensitive potassium channel (sKATP), composed primarily of Kir6.2 and SUR2A subunits, has been implicated in cardiac myocyte volume regulation during stress; however, it is not involved in cardioprotection by the KATP channel opener diazoxide. Paradoxically, the sKATP channel subunit Kir6.2 is necessary for detrimental myocyte swelling secondary to stress. The Kir6.1 subunit may also contribute to KATP channels in the heart, and we hypothesized that this subunit may play a role in myocyte volume regulation in response to stress. Study Design Isolated cardiac myocytes from either wild type mice (WT) or mice lacking the Kir6.1 subunit (Kir6.1(−/−)) were exposed to control Tyrode’s solution (TYR) for 20 min, test solution (TYR, hypothermic hyperkalemic cardioplegia (CPG), or CPG + KATP channel opener diazoxide (CPG + DZX)) for 20 min, followed by TYR for 20 min. Myocyte volume and contractility were measured and analyzed. Results Both WT and Kir6.1(−/−) myocytes demonstrated significant swelling during exposure to stress (CPG) that was prevented by DZX. WT myocytes also demonstrated reduced contractility during stress of cardioplegia that was prevented by DZX. However, Kir6.1(−/−) myocytes did not show reduced contractility during stress. Conclusions These data indicate that KATP channel subunit Kir6.1 is not necessary for diazoxide’s maintenance of cell volume during the stress of cardioplegia. The absence of Kir6.1 does not affect the contractile properties of myocytes during stress suggesting the absence of Kir6.1 improves myocyte tolerance to stress via an unknown mechanism.

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ATP‐Sensitive Potassium Channels and Their Physiological and Pathophysiological Roles

Tinker

Aziz

et al. 2018

Comprehensive Physiology

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ATP sensitive potassium channels (K ) are so named because they open as cellular ATP levels fall. This leads to membrane hyperpolarization and thus links cellular metabolism to membrane excitability. They also respond to MgADP and are regulated by a number of cell signaling pathways. They have a rich and diverse pharmacology with a number of agents acting as specific inhibitors and activators. K channels are formed of pore-forming subunits, Kir6.1 and Kir6.2, and a large auxiliary subunit, the sulfonylurea receptor (SUR1, SUR2A, and SUR2B). The Kir6.0 subunits are a member of the inwardly rectifying family of potassium channels and the sulfonylurea receptor is part of the ATP-binding cassette family of proteins. Four SURs and four Kir6.x form an octameric channel complex and the association of a particular SUR with a specific Kir6.x subunit constitutes the K current in a particular tissue. A combination of mutagenesis work combined with structural studies has identified how these channels work as molecular machines. They have a variety of physiological roles including controlling the release of insulin from pancreatic β cells and regulating blood vessel tone and blood pressure. Furthermore, mutations in the genes underlie human diseases such as congenital diabetes and hyperinsulinism. Additionally, opening of these channels is protective in a number of pathological conditions such as myocardial ischemia and stroke. © 2018 American Physiological Society. Compr Physiol 8:1463-1511, 2018.

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Role of the Sarcolemmal Adenosine Triphosphate–Sensitive Potassium Channel in Hyperkalemic Cardioplegia-Induced Myocyte Swelling and Reduced Contractility

Cited by 20 publications

References 24 publications

Diazoxide Cardioprotection Is Independent of Adenosine Triphosphate-Sensitive Potassium Channel Kir 6.1 Subunit in Response to Stress

Diazoxide Cardioprotection Is Independent of Adenosine Triphosphate-Sensitive Potassium Channel Kir 6.1 Subunit in Response to Stress

Diazoxide Cardioprotection Is Independent of Adenosine Triphosphate-Sensitive Potassium Channel Kir6.1 Subunit in Response to Stress

ATP‐Sensitive Potassium Channels and Their Physiological and Pathophysiological Roles

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