Nicorandil, an ATP-sensitive potassium channel activation, attenuates myocardial injury in rats with ischemic cardiomyopathy

Muskrats (Ondontra zibethicus) are common freshwater diving mammals exhibiting a bradycardia with both forced and voluntary diving. This bradycardia is mediated by vagal innervation; however, if hypoxia is present there may be local factors that also decrease heart rate. Some of these local factors may include ATP-sensitive potassium channel activation and extracellular accumulation of potassium ions, hydrogen ions and lactate. The purpose of this study was to investigate the role of these factors in the isolated perfused hearts of muskrats and of a non-diving mammal, the guinea pig. Although lactate and proton administration reduced heart rate in isolated muskrat and guinea pig hearts, there was no difference in the response to lactate and proton infusion between the two species. Muskrat hearts were more sensitive to the heart-rate-lowering effects of exogenously applied potassium than were guinea pig hearts. Early increases in extracellular potassium concentration during hypoxia are thought to be mediated by the ATP-sensitive potassium channel. Activation of these channels under normoxic conditions had a mildly negative chronotropic effect in both species; however, activation of these channels with Lemakalim under hypoxic conditions caused the guinea pig heart to respond with an augmented bradycardia similar to that seen in the hypoxic muskrat heart in the absence of drugs. Inhibition of these channels by glibenclamide during hypoxia was partially successful in blocking the bradycardia in guinea pig hearts, but inhibition of the same channels in hypoxic muskrat hearts had a damaging effect as two of five hearts went into contracture during the hypoxia. Thus, although ATP-sensitive potassium channels appear to have a major role in the bradycardia of hypoxia in guinea pigs, the failure to prevent the bradycardia by inhibition of these channels in muskrat hearts suggests that multiple factors are involved in the hypoxia-induced bradycardia in this species.

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Effects of mitochondrial ATP-sensitive potassium channel activation (nicorandil) in patients with angina pectoris undergoing elective percutaneous coronary interventions

Medicine ◽

10.1097/md.0000000000014165 ◽

2019 ◽

Vol 98 (3) ◽

pp. e14165 ◽

Cited By ~ 3

Author(s):

Houyong Zhu ◽

Xiaoqun Xu ◽

Xiaojiang Fang ◽

Jianwu Zheng ◽

Tielong Chen ◽

...

Keyword(s):

Angina Pectoris ◽

Potassium Channel ◽

Percutaneous Coronary Interventions ◽

Channel Activation ◽

Coronary Interventions ◽

Percutaneous Coronary

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K v7 potassium channel activation with ICA ‐105665 reduces photoparoxysmal EEG responses in patients with epilepsy

Epilepsia ◽

10.1111/epi.12224 ◽

2013 ◽

Vol 54 (8) ◽

pp. 1437-1443 ◽

Cited By ~ 14

Author(s):

Dorotheé G. A. Kasteleijn‐Nolst Trenité ◽

Victor Biton ◽

Jacqueline A. French ◽

Bassel Abou‐Khalil ◽

William E. Rosenfeld ◽

...

Keyword(s):

Potassium Channel ◽

Channel Activation ◽

Patients With Epilepsy

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Differential Modulation of the Cardiac Adenosine Triphosphate-sensitive Potassium Channel by Isoflurane and Halothane

Anesthesiology ◽

10.1097/00000542-200207000-00008 ◽

2002 ◽

Vol 97 (1) ◽

pp. 50-56 ◽

Cited By ~ 30

Author(s):

Wai-Meng Kwok ◽

Anne T. Martinelli ◽

Kazuhiro Fujimoto ◽

Akihiro Suzuki ◽

Anna Stadnicka ◽

...

Keyword(s):

Potassium Channel ◽

Adenosine Triphosphate ◽

Volatile Anesthetic ◽

Volatile Anesthetics ◽

Dependent Manner ◽

Patch Clamp Technique ◽

Channel Activation ◽

Beneficial Effects ◽

Channel Current ◽

Channel Opening

Background The cardiac adenosine triphosphate-sensitive potassium (K(ATP)) channel is activated during pathophysiological episodes such as ischemia and hypoxia and may lead to beneficial effects on cardiac function. Studies of volatile anesthetic interactions with the cardiac K(ATP) channel have been limited. The goal of this study was to investigate the ability of volatile anesthetics halothane and isoflurane to modulate the cardiac sarcolemmal K(ATP) channel. Methods The K(ATP) channel current (I(KATP)) was monitored using the whole cell configuration of the patch clamp technique from single ventricular cardiac myocytes enzymatically isolated from guinea pig hearts. I(KATP) was elicited by extracellular application of the potassium channel openers 2,4-dinitrophenol or pinacidil. Results Volatile anesthetics modulated I(KATP) in an anesthetic-dependent manner. Isoflurane facilitated the opening of the K(ATP) channel. Following initial activation of I(KATP) by 2,4-dinitrophenol, isoflurane at 0.5 and 1.3 mm further increased current amplitude by 40.4 +/- 11.1% and 58.4 +/- 20.6%, respectively. Similar results of isoflurane were obtained when pinacidil was used to activate I(KATP). However, isoflurane alone was unable to elicit K(ATP) channel opening. In contrast, halothane inhibited I(KATP) elicited by 2,4-dinitrophenol by 50.6 +/- 5.8% and 72.1 +/- 11.6% at 0.4 and 1.0 mm, respectively. When I(KATP) was activated by pinacidil, halothane had no significant effect on the current. Conclusions The cardiac sarcolemmal K(ATP) channel is differentially modulated by volatile anesthetics. Isoflurane can facilitate the further opening of the K(ATP) channel following initial channel activation by 2,4-dinitrophenol or pinacidil. The effect of halothane was dependent on the method of channel activation, inhibiting I(KATP) activated by 2,4-dinitrophenol but not by pinacidil.

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