Isoflurane Sensitizes the Cardiac Sarcolemmal Adenosine Triphosphate–Sensitive Potassium Channel to Pinacidil

Gassmayr, Susanne; Stadnicka, Anna; Suzuki, Akihiro; Kwok, Wai‐Meng; Bošnjak, Željko J.

doi:10.1097/00000542-200301000-00020

Cited by 18 publications

(14 citation statements)

References 29 publications

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“…Figure 1A illustrates the stable time course of wholecell currents elicited by test pulses from Ϫ40 mV to 0 mV during prolonged intracellular dialysis with 1.0 mM of ATP. The subsequent addition of 1 mM of isoflurane did not activate I KATP , as we previously reported in this model (17)(18)(19). However, as shown in Figure 1B, pretreatment with the PKC activator PMA (0.2 M), which alone did not elicit sarcK ATP channel activation, facilitated or primed the channels for activation of I KATP by later exposure to isoflurane.…”

Section: Methodssupporting

confidence: 80%

“…Pretreatment with the phorbol ester PMA, which itself did not elicit I KATP , altered channel function to facilitate I KATP activation during later isoflurane exposure, although isoflurane alone (without stimulation of PKC) does not activate the channels (17)(18)(19). The role of PKC in these actions regulating I KATP was confirmed by findings that the PKC antagonist bisindolylmaleimide prevented the actions of PMA, facilitating isofluraneinduced I KATP , as well as preventing activation of I KATP when superfused just before a second isoflurane challenge.…”

Section: Discussionmentioning

confidence: 99%

“…Our studies in isolated guinea pig cardiomyocytes have shown that isoflurane facilitates the opening of sarcK ATP channels during metabolic inhibition or by the K ATP channel opener pinacidil at a reduced intracellular ATP concentration achieved by dialysis with a patch pipette (17)(18)(19). We also found that isoflurane did not facilitate the opening of sarcK ATP channels in excised membrane patches, but isoflurane would facilitate activation of whole-cell sarcK ATP current (I KATP ) in a model of a test ischemia in which PKC was stimulated by a phorbol ester during the reduction of intracellular ATP by dialysis (18).…”

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confidence: 96%

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The Interaction of Isoflurane and Protein Kinase C-Activators on Sarcolemmal KATP Channels

Turner

Fujimoto²,

Suzuki³

et al. 2005

Anesthesia & Analgesia

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Protein kinase C (PKC)-dependent signaling pathways may be involved in the "memory" effect of anesthetic and ischemic preconditioning, which facilitates activation of cardioprotective adenosine triphosphate (ATP)-sensitive potassium channels during later ischemic challenge and ATP depletion. Using patch-clamp techniques, we found that exposure of isolated guinea pig cardiomyocytes to 1 mM of isoflurane after phorbol ester stimulation of PKC facilitates the induction of larger (P < or = 0.05) sarcolemmal K(ATP) channel currents (IKATP) during cell dialysis with 0.5, compared to 1.0, mM of ATP in the pipette (10 +/- 5 versus 2 +/- 1 pA/pF in five and six cells, respectively). A PKC inhibitor, bisindolylmaleimide, abolished the induction of IKATP by a second brief isoflurane exposure under these conditions. A diacylglycerol PKC activator applied via the pipette elicited concentration-related activation of IKATP. The diacylglycerol alone (0.5 microM) elicited I(KATP), averaging 5 +/- 3 pA/pF in nine cells. Briefly treating myocytes on the microscope stage with isoflurane, followed by washout and patching with the same diacylglycerol solution, elicited larger (P < or = 0.01) IKATP, averaging 40 +/- 9 pA/pF (10 cells), with an onset 48 +/- 2 min after anesthetic pretreatment. Facilitation of IKATP by isoflurane during the reduction of intracellular ATP is dependent on PKC, whereas "preconditioning" myocytes with isoflurane causes persistent changes in sarcolemmal KATP channel function, which enhance the induction of IKATP by a diacylglycerol.

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Section: Methodssupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 96%

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The Interaction of Isoflurane and Protein Kinase C-Activators on Sarcolemmal KATP Channels

Turner

Fujimoto²,

Suzuki³

et al. 2005

Anesthesia & Analgesia

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“…A 1 receptor activity modified by isoflurane could possibly be a trigger for K ATP channel activation leading to the development of cerebral ischemic tolerance. This inhalational anesthetic preconditioning mechanism has been observed in myocardial ischemia (Gassmayr et al, 2003;Roscoe et al, 2000) but is unproven in ischemic brain.…”

Section: Adenosine a 1 Receptor Activationmentioning

confidence: 95%

Inhalational Anesthetics as Neuroprotectants or Chemical Preconditioning Agents in Ischemic Brain

Kitano

Kirsch

Hurn

et al. 2006

J Cereb Blood Flow Metab

179

128

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This review will focus on inhalational anesthetic neuroprotection during cerebral ischemia and inhalational anesthetic preconditioning before ischemic brain injury. The limitations and challenges of past and current research in this area will be addressed before reviewing experimental and clinical studies evaluating the effects of inhalational anesthetics before and during cerebral ischemia. Mechanisms underlying volatile anesthetic neuroprotection and preconditioning will also be examined. Lastly, future directions for inhalational anesthetics and ischemic brain injury will be briefly discussed.

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“…A decrease in intracellular pH has also been shown to enhance the effects of isoflurane by reducing the channel's sensitivity to intracellular ATP [27]. Another reported effect of isoflurane is its ability to sensitize the sarcKATP channel to pinacidil [28].…”

Section: Atp-sensitive K Channelmentioning

confidence: 99%

The yin and yang of volatile anesthetic action on cardiac potassium channels

Kwok

2005

International Congress Series

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Isoflurane Sensitizes the Cardiac Sarcolemmal Adenosine Triphosphate–Sensitive Potassium Channel to Pinacidil

Cited by 18 publications

References 29 publications

The Interaction of Isoflurane and Protein Kinase C-Activators on Sarcolemmal KATP Channels

The Interaction of Isoflurane and Protein Kinase C-Activators on Sarcolemmal KATP Channels

Inhalational Anesthetics as Neuroprotectants or Chemical Preconditioning Agents in Ischemic Brain

The yin and yang of volatile anesthetic action on cardiac potassium channels

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