			Home About us Contact

Sarcolemmal KATP Channels (sarcolemmal + katp_channel)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Cardioprotection afforded by chronic exercise is mediated by the sarcolemmal, and not the mitochondrial, isoform of the KATP channel in the rat

THE JOURNAL OF PHYSIOLOGY, Issue 3 2005
David A. Brown
This study was conducted to examine the role of myocardial ATP-sensitive potassium (KATP) channels in exercise-induced protection from ischaemia,reperfusion (I,R) injury. Female rats were either sedentary (Sed) or exercised for 12 weeks (Tr). Hearts were excised and underwent a 1,2 h regional I,R protocol. Prior to ischaemia, hearts were subjected to pharmacological blockade of the sarcolemmal KATP channel with HMR 1098 (SedHMR and TrHMR), mitochondrial blockade with 5-hydroxydecanoic acid (5HD; Sed5HD and Tr5HD), or perfused with buffer containing no drug (Sed and Tr). Infarct size was significantly smaller in hearts from Tr animals (35.4 ± 2.3 versus 44.7 ± 3.0% of the zone at risk for Tr and Sed, respectively). Mitochondrial KATP blockade did not abolish the training-induced infarct size reduction (30.0 ± 3.4 versus 38.0 ± 2.6 in Tr5HD and Sed5HD, respectively); however, sarcolemmal KATP blockade completely eradicated the training-induced cardioprotection. Infarct size was 71.2 ± 3.3 and 64.0 ± 2.4% of the zone at risk for TrHMR and Sed HMR. The role of sarcolemmal KATP channels in Tr-induced protection was also supported by significant increases in both subunits of the sarcolemmal KATP channel following training. LV developed pressure was better preserved in hearts from Tr animals, and was not influenced by addition of HMR 1098. 5HD decreased pressure development regardless of training status, from 15 min of ischaemia through the duration of the protocol. This mechanical dysfunction was likely to be due to a 5HD-induced increase in myocardial Ca2+ content following I,R. The major findings of the present study are: (1) unlike all other known forms of delayed cardioprotection, infarct sparing following chronic exercise was not abolished by 5HD; (2) pharmacological blockade of the sarcolemmal KATP channel nullified the cardioprotective benefits of exercise training; and (3) increased expression of sarcolemmal KATP channels was observed following chronic training. [source]

Roles of KATP channels in delayed cardioprotection and intracellular Ca2+ in the rat heart as revealed by , -opioid receptor stimulation with U50,488H

BRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2003
Mai Chen
The effect of preconditioning with U50,488 H (UP), a selective kappa-opioid receptor (, -OR) agonist, on infarct size and intracellular Ca2+ ([Ca2+]i) in the heart subjected to ischaemic insults were studied and evaluated. U50,488 H administered intravenously reduced the infarct size 18,48 h after administration in isolated hearts subjected to regional ischaemia/reperfusion (I/R). The effect was dose dependent. A peak effect was reached at 10 mg kg,1 U50,488 H and at 24 h after administration. The effect of 10 mg kg,1 U50,488 H at 24 h after administration was abolished by nor-binaltorphimine (nor-BNI), a selective , -OR antagonist, indicating the effect was , -OR mediated. The infarct reducing effect of U50,488 H was attenuated when a selective blocker of mitochondrial (5-hydroxydecanoic acid, 5-HD) or sarcolemmal (HRM-1098) ATP-sensitive potassium channel (KATP) was coadministered with U50,488 H 24 h before ischaemia or when 5-HD was administered just before ischaemia. U50,488 H also attenuated the elevation in [Ca2+]i and reduction in electrically induced [Ca2+]i transient in cardiomyocytes subjected to ischaemic insults. The effects were reversed by blockade of KATP channel, which abolished the protective effect of preconditioning with U50,488 H. The results indicated that mitochondrial KATP channel serves as both a trigger and a mediator, while sarcolemmal KATP channel as a trigger only, of delayed cardioprotection of , -OR stimulation. The effects of these channels may result from prevention/attenuation of [Ca2+]i overload induced by ischaemic insults. British Journal of Pharmacology (2003) 140, 750,758. doi:10.1038/sj.bjp.0705475 [source]

Femininity and sarcolemmal KATP channels: a matter of the heart and the heart of the matter

THE JOURNAL OF PHYSIOLOGY, Issue 23 2009
Aleksandar Jovanovi, Article first published online: 30 NOV 200
No abstract is available for this article. [source]

Cardioprotection afforded by chronic exercise is mediated by the sarcolemmal, and not the mitochondrial, isoform of the KATP channel in the rat

Mechanisms of Preventive Effect of Nicorandil on Ischaemia-Induced Ventricular Tachyarrhythmia in Isolated Arterially Perfused Canine Left Ventricular Wedges

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2008
Masamichi Hirose
We examined effects of nicorandil on the induction of VT during acute myocardial ischaemia. Optical action potentials were recorded from the entire transmural wall of arterially perfused canine left ventricular wedges. Ischaemia was produced by arterial occlusion for 20 min. During endocardial pacing, nicorandil shortened mean action potential duration (APD) in the transmural wall before ischaemia and further shortened it during ischaemia without increasing dispersion of APD. HMR1098, a selective blocker of sarcolemmal ATP-sensitive K+ channels, inhibited the shortening of APD by nicorandil before and during ischaemia. Ischaemia decreased transmural conduction velocity (CV). Nicorandil partially restored CV to a similar extent in the absence and presence of HMR1098. In contrast, HMR1098 did not suppress the ischaemic conduction slowing in the absence of nicorandil. Nicorandil suppressed the increased dispersion of local CV during ischaemia. Isochrone maps on the initiation of VT showed that reentry in the transmural surface resulted from the excitation of the epicardial region of transmural surface. Nicorandil significantly increased the size of non-excited area in the epicardial region of the transmural wall, thereby significantly reducing the incidence of VT induced during ischaemia. HMR1098 inhibited this effect of nicorandil. These results suggest that nicorandil prevents VT during acute global ischaemia primarily by augmenting the inactivation of epicardial muscle through the activation of sarcolemmal KATP channels. [source]

A Patient Suffering from Hypokalemic Periodic Paralysis Is Deficient in Skeletal Muscle ATP-sensitive K+ channels

CLINICAL AND TRANSLATIONAL SCIENCE, Issue 1 2008
Sofija Jovanovi
Abstract Hypokalemic periodic paralysis (HOPP) is a rare disease associated with attacks of muscle weakness and hypokalemia. In the present study, immunoprecipitation/Western blotting has shown that a HOPP patient was deficient in sarcolemmal KATP channels. Real-time RT-PCR has revealed that HOPP has decreased mRNA levels of Kir6.2, a pore-forming KATP channel subunit, without affecting the expression of other KATP channel-forming proteins. Based on these findings, we conclude that HOPP could be associated with impaired expression of Kir6.2 which leads to deficiency in skeletal muscle KATP channels, which may explain the symptoms and clinical signs of this disease. [source]