Voltage-dependent ATP-sensitive potassium channels of skeletal muscle membrane

Spruce, A. E.; Standen, N B; Stanfield, Peter

doi:10.1038/316736a0

Cited by 396 publications

(221 citation statements)

References 16 publications

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“…This concept is supported by the observations that carnitine transport is stimulated by preloading the vesicles with K 1 and that a small additional stimulation is observed in the presence of valinomycin. As skeletal muscle contains ATP-dependent K 1 channels which are open in the absence of ATP [54], K 1 will diffuse out of vesicles preloaded with K 1 , creating an inside negative diffusion potential. This concept explains why preloading the vesicles with K 1 stimulates uptake of carnitine and also why the effect of valinomycin is only small.…”

Section: Discussionmentioning

confidence: 99%

Characterization of L‐carnitine transport into rat skeletal muscle plasma membrane vesicles

Berardi¹,

Stieger²,

Hagenbuch³

et al. 2000

European Journal of Biochemistry

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Transport of l-carnitine into skeletal muscle was investigated using rat sarcolemmal membrane vesicles. In the presence of an inwardly directed sodium chloride gradient, l-carnitine transport showed a clear overshoot. The uptake of l-carnitine was increased, when vesicles were preloaded with potassium. When sodium was replaced by lithium or cesium, and chloride by nitrate or thiocyanate, transport activities were not different from in the presence of sodium chloride. However, l-carnitine transport was clearly lower in the presence of sulfate or gluconate, suggesting potential-dependent transport. An osmolarity plot revealed a positive slope and a significant intercept, indicating transport of l-carnitine into the vesicle lumen and binding to the vesicle membrane. Displacement experiments revealed that approximately 30% of the l-carnitine associated with the vesicles was bound to the outer and 30% to the inner surface of the vesicle membrane, whereas 40% was unbound inside the vesicle. Saturable transport could be described by Michaelis±Menten kinetics with an apparent K m of 13.1 mm and a V max of 2.1 pmol´(mg protein 21 )´s 21 . l-Carnitine transport could be trans-stimulated by preloading the vesicles with l-carnitine but not with the carnitine precursor butyrobetaine, and was cis-inhibited by l-palmitoylcarnitine, l-isovalerylcarnitine, and glycinebetaine. On comparing carnitine transport into rat kidney brush-border membrane vesicles and OCTN2, a sodium-dependent high-affinity human carnitine transporter, cloned recently from human kidney also expressed in muscle, the K m values are similar but driving forces, pattern of inhibition and stereospecificity are different. This suggests the existence of more than one carnitine carrier in skeletal muscle.

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Section: Discussionmentioning

confidence: 99%

Characterization of L‐carnitine transport into rat skeletal muscle plasma membrane vesicles

Berardi¹,

Stieger²,

Hagenbuch³

et al. 2000

European Journal of Biochemistry

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“…These so-called ATPsensitive potassium (K ATP ) channels were suggested to play a cardioprotective role during ischaemia. Later, K ATP channels were also found in skeletal muscle [2], smooth muscle [3] and pancreatic beta cells [4] from animals. In pancreatic beta cells the K ATP channels mediate insulin secretion [5] and are a target for sulphonylurea derivatives in the treatment of non-insulin-dependent diabetes mellitus (NIDDM) [6].…”

mentioning

confidence: 99%

Blockade of vascular ATP-sensitive potassium channels reduces the vasodilator response to ischaemia in humans

et al. 1996

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In 1983, Noma [1] was the first to describe that an outward potassium current increased significantly when guinea pig or rabbit cardiac muscle cells were subjected to hypoxia. This current was caused by the activation of potassium channels, which was independent of the intracellular Ca 2+ concentration, but dependent on the intracellular concentration of adenosine-5 ′-triphosphate ([ATP] i ). These so-called ATPsensitive potassium (K ATP ) channels were suggested to play a cardioprotective role during ischaemia. Later, K ATP channels were also found in skeletal muscle [2], smooth muscle [3] and pancreatic beta cells [4] from animals. In pancreatic beta cells the K ATP channels mediate insulin secretion [5] and are a target for sulphonylurea derivatives in the treatment of non-insulin-dependent diabetes mellitus (NIDDM) [6]. Sulphonylurea derivatives are highly specific in blocking pancreatic and cardiovascular K ATP channels, and Diabetologia (1996Diabetologia ( ) 39: 1562Diabetologia ( -1568 Blockade of vascular ATP-sensitive potassium channels reduces the vasodilator response to ischaemia in humans Summary Experimental data show that ATP-sensitive potassium (K ATP ) channels not only occur in pancreatic beta cells, but also in the cardiovascular system, where they mediate important cardioprotective mechanisms. Sulphonylurea derivatives can block the cardiovascular K ATP channels and may therefore interfere with these cardioprotective mechanisms. Therefore, it is of clinical importance to investigate whether sulphonylurea derivatives interact with vascular K ATP channels in humans. Using venous-occlusion strain-gauge plethysmography, we investigated whether ischaemia-induced reactive hyperaemia is reduced by the sulphonylurea derivative glibenclamide in 12 healthy male non-smoking volunteers. Forearm vasodilator responses to three periods of arterial occlusion (2, 5 and 13 min) during concomitant infusion of placebo into the brachial artery were compared with responses during concomitant intra-arterial infusion of glibenclamide (0.33A control study (n = 6) showed that time itself did not change the vasodilator response to ischaemia.Glibenclamide significantly increased minimal vascular resistance (from 2.1 ± 0.1 to 2.3 ± 0.2 arbitrary units, Student's t-test: p = 0.01), and reduced mean forearm blood flow (from 37.5 ± 2.0 to 35.4 ± 2.0 ml ⋅ min -1 ⋅ dl -1 after 13 min occlusion, ANOVA with repeated measures: p = 0.006) and flow debt repayment during the first reperfusion minute (ANOVA with repeated measures: p = 0.04). In contrast, total flow debt repayment was not affected. Infusion of glibenclamide into the brachial artery resulted in local concentrations in the clinically relevant range, whereas the systemic concentration remained too low to elicit hypoglycaemic effects. Our results suggest that therapeutic concentrations of glibenclamide induce a slight but significant reduction in the early and peak vasodilation during reactive hyperaemia.

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“…These channels were later identified in many other tissues, including the skeletal muscle [7] , smooth K ATP channel genes The Kir6 subfamily is a member of the weak inward rectifier family and has two members, Kir6.1 and Kir6.2. The Kir6.2 gene (KCNJ11) in humans is located on chromosome 11.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective role of ATP-sensitive potassium channels in cerebral ischemia

Sun

Feng

2012

Acta Pharmacol Sin

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ATP-sensitive potassium (K ATP ) channels are weak, inward rectifiers that couple metabolic status to cell membrane electrical activity, thus modulating many cellular functions. An increase in the ADP/ATP ratio opens K ATP channels, leading to membrane hyperpolarization. K ATP channels are ubiquitously expressed in neurons located in different regions of the brain, including the hippocampus and cortex. Brief hypoxia triggers membrane hyperpolarization in these central neurons. In vivo animal studies confirmed that knocking out the Kir6.2 subunit of the K ATP channels increases ischemic infarction, and overexpression of the Kir6.2 subunit reduces neuronal injury from ischemic insults. These findings provide the basis for a practical strategy whereby activation of endogenous K ATP channels reduces cellular damage resulting from cerebral ischemic stroke. K ATP channel modulators may prove to be clinically useful as part of a combination therapy for stroke management in the future.

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Voltage-dependent ATP-sensitive potassium channels of skeletal muscle membrane

Cited by 396 publications

References 16 publications

Characterization of L‐carnitine transport into rat skeletal muscle plasma membrane vesicles

Characterization of L‐carnitine transport into rat skeletal muscle plasma membrane vesicles

Blockade of vascular ATP-sensitive potassium channels reduces the vasodilator response to ischaemia in humans

Neuroprotective role of ATP-sensitive potassium channels in cerebral ischemia

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