Nutrigenomics of inward rectifier potassium channels

Ferreira, Gonzalo; Santander, Axel; Cardozo, Romina; Chavarría, Luisina; Domínguez, Lucía; Mujica, Nicolás; Benítez, Milagros; Sastre, Santiago; Sobrevía, Luis; Nicolson, Garth L.

doi:10.1016/j.bbadis.2023.166803

Cited by 2 publications

(1 citation statement)

References 239 publications

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“…Inwardly rectifying potassium channels are an important class of potassium channels, which are characterized by opening when the membrane is hyperpolarized and producing inward potassium currents, which are mainly involved in maintaining the resting membrane potential and hyperpolarization of cells, and directly affect the action potential, time period and morphology, and thus play an important role in the regulation of neuronal activity (Ferreira et al 2023 ; Martelli 2018 ). It is reported that Ba 2+ , a non-selective inward rectifier potassium (KIR) channel blocker, induced a small depolarization of POMC neurons (Smith et al 2007 ).…”

Section: Introductionmentioning

confidence: 99%

Hypothalamic POMC neuron-specific knockout of MC4R affects insulin sensitivity by regulating Kir2.1

Guo,

Xin,

Wang

et al. 2024

Mol Med

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Background Imbalance in energy regulation is a major cause of insulin resistance and diabetes. Melanocortin-4 receptor (MC4R) signaling at specific sites in the central nervous system has synergistic but non-overlapping functions. However, the mechanism by which MC4R in the arcuate nucleus (ARC) region regulates energy balance and insulin resistance remains unclear. Methods The MC4Rflox/flox mice with proopiomelanocortin (POMC) -Cre mice were crossed to generate the POMC-MC4Rflox/+ mice. Then POMC-MC4Rflox/+ mice were further mated with MC4Rflox/flox mice to generate the POMC-MC4Rflox/flox mice in which MC4R is selectively deleted in POMC neurons. Bilateral injections of 200 nl of AAV-sh-Kir2.1 (AAV-sh-NC was used as control) were made into the ARC of the hypothalamus. Oxygen consumption, carbon dioxide production, respiratory exchange ratio and energy expenditure were measured by using the CLAMS; Total, visceral and subcutaneous fat was analyzed using micro-CT. Co-immunoprecipitation assays (Co-IP) were used to analyze the interaction between MC4R and Kir2.1 in GT1-7 cells. Results POMC neuron-specific ablation of MC4R in the ARC region promoted food intake, impaired energy expenditure, leading to increased weight gain and impaired systemic glucose homeostasis. Additionally, MC4R ablation reduced the activation of POMC neuron, and is not tissue-specific for peripheral regulation, suggesting the importance of its central regulation. Mechanistically, sequencing analysis and Co-IP assay demonstrated a direct interaction of MC4R with Kir2.1. Knockdown of Kir2.1 in POMC neuron-specific ablation of MC4R restored the effect of MC4R ablation on energy expenditure and systemic glucose homeostasis, indicating by reduced body weight and ameliorated insulin resistance. Conclusion Hypothalamic POMC neuron-specific knockout of MC4R affects energy balance and insulin sensitivity by regulating Kir2.1. Kir2.1 represents a new target and pathway that could be targeted in obesity.

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Section: Introductionmentioning

confidence: 99%

Hypothalamic POMC neuron-specific knockout of MC4R affects insulin sensitivity by regulating Kir2.1

Guo,

Xin,

Wang

et al. 2024

Mol Med

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The network of cardiac KIR2.1: its function, cellular regulation, electrical signaling, diseases and new drug avenues

Li,

van der Heyden

2024

Naunyn-Schmiedeberg's Arch Pharmacol

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The functioning of the human heart relies on complex electrical and communication systems that coordinate cardiac contractions and sustain rhythmicity. One of the key players contributing to this intricate system is the KIR2.1 potassium ion channel, which is encoded by the KCNJ2 gene. KIR2.1 channels exhibit abundant expression in both ventricular myocytes and Purkinje fibers, exerting an important role in maintaining the balance of intracellular potassium ion levels within the heart. And by stabilizing the resting membrane potential and contributing to action potential repolarization, these channels have an important role in cardiac excitability also. Either gain- or loss-of-function mutations, but also acquired impairments of their function, are implicated in the pathogenesis of diverse types of cardiac arrhythmias. In this review, we aim to elucidate the system functions of KIR2.1 channels related to cellular electrical signaling, communication, and their contributions to cardiovascular disease. Based on this knowledge, we will discuss existing and new pharmacological avenues to modulate their function.

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Nutrigenomics of inward rectifier potassium channels

Cited by 2 publications

References 239 publications

Hypothalamic POMC neuron-specific knockout of MC4R affects insulin sensitivity by regulating Kir2.1

Hypothalamic POMC neuron-specific knockout of MC4R affects insulin sensitivity by regulating Kir2.1

The network of cardiac KIR2.1: its function, cellular regulation, electrical signaling, diseases and new drug avenues

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