ATP-Sensitive Potassium Channel Traffic Regulation by Adenosine and Protein Kinase C

Hu, Keli; Huang, Cindy Shen; Jan, Yuh Nung

doi:10.1016/s0896-6273(03)00256-3

Cited by 109 publications

(141 citation statements)

References 85 publications

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“…Constructs-The Kir6.2 sequence containing an HA tag and an 11-amino acid linker was used as "WT" Kir6.2 (30) and served as a template to generate the following mutant constructs using QuikChange II Site-directed Mutagenesis kit (Stratagene): Kir6.2⌬26-HA, Kir6.2⌬36-HA, Kir6.2T180A-HA, Kir6.2T224A-HA, Kir6.2T224E-HA, and Kir6.2Y330C-HA. The Kir6.2T180A-HA construct was used as a template to generate Kir6.2A180T-HA.…”

Section: Methodsmentioning

confidence: 99%

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Regulation of Cardiac ATP-sensitive Potassium Channel Surface Expression by Calcium/Calmodulin-dependent Protein Kinase II

Sierra

Zhu

Sapay

et al. 2013

Journal of Biological Chemistry

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Background: Surface expression of cardiac ATP-sensitive potassium (K ATP ) channels impacts cellular energy homeostasis. Results: Activation of calcium/calmodulin-dependent protein kinase II (CaMKII) results in K ATP channel internalization, requiring specific motifs on the Kir6.2 channel subunit. Conclusion: CaMKII phosphorylation of Kir6.2 promotes endocytosis of cardiac K ATP channels. Significance: This mechanism reveals new targets to improve cardiac energy efficiency and stress resistance.

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Section: Methodsmentioning

confidence: 99%

“…Dominant-negative dynamin and scrambled control were synthesized (bioSYNTHESIS) according to the published sequence (30).…”

Section: Methodsmentioning

confidence: 99%

Regulation of Cardiac ATP-sensitive Potassium Channel Surface Expression by Calcium/Calmodulin-dependent Protein Kinase II

Sierra

Zhu

Sapay

et al. 2013

Journal of Biological Chemistry

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“…Lactate modulates the ATP sensitivity of K ATP channels and would accumulate in the vicinity of LDH, and thus of cardiac K ATP channels, under anaerobic conditions [100]. Other examples include direct channel effects of G protein subunits [101,102], changes in the composition of membrane phospholipids that interact with Kir6.2 to modulate pore function [103,104], activation of the protein kinase systems PKC and PKA with channel effects through phosphorylation/dephosphorylation [105][106][107][108], and pH effects through protonation of channel proteins [109].…”

Section: The K Atp Channel Complex As a Component Of The Cellular Enementioning

confidence: 99%

ATP-sensitive K channel channel/enzyme multimer: Metabolic gating in the heart

Alekseev

Hodgson

Karger

et al. 2005

Journal of Molecular and Cellular Cardiology

108

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Cardiac ATP-sensitive K + (K ATP ) channels, gated by cellular metabolism, are formed by association of the inwardly rectifying potassium channel Kir6.2, the potassium conducting subunit, and SUR2A, the ATP-binding cassette protein that serves as the regulatory subunit. Kir6.2 is the principal site of ATP-induced channel inhibition, while SUR2A regulates K + flux through adenine nucleotide binding and catalysis. The ATPase-driven conformations within the regulatory SUR2A subunit of the K ATP channel complex have determinate linkage with the states of the channel's pore. The probability and life-time of ATPase-induced SUR2A intermediates, rather than competitive nucleotide binding alone, defines nucleotide-dependent K ATP channel gating. Cooperative interaction, instead of independent contribution of individual nucleotide binding domains within the SUR2A subunit, serves a decisive role in defining K ATP channel behavior. Integration of K ATP channels with the cellular energetic network renders these channel/enzyme heteromultimers high-fidelity metabolic sensors. This vital function is facilitated through phosphotransfer enzyme-mediated transmission of controllable energetic signals. By virtue of coupling with cellular energetic networks and the ability to decode metabolic signals, K ATP channels set membrane excitability to match demand for homeostatic maintenance. This new paradigm in the operation of an ion channel multimer is essential in providing the basis for K ATP channel function in the cardiac cell, and for understanding genetic defects associated with life-threatening diseases that result from the inability of the channel complex to optimally fulfill its physiological role.

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“…Although there are no data for ␤-cells, studies of cardiac and neuronal cells have demonstrated that activation of PKC 3 down-regulates K ATP channels (22). Given the evidence that PKC enzymes in the ␤-cell are activated by glucose stimulation (23,24) and that activation of PKC augments insulin secretion (23,25,26), it is reasonable to speculate that PKC could down-regulate the number of K ATP channels in ␤-cells, thereby enhancing ␤-cell excitability and insulin secretion.…”

mentioning

confidence: 99%

“…It is therefore not surprising that endocytic mechanisms are often targeted by cellular signals, such as protein kinases, to regulate the density of membrane proteins at the plasma membrane (29,30,33). Hu et al (22) reported that activation of PKC stimulates endocytosis of K ATP channels and that little or no channel internalization occurs in the absence of PKC stimulation. However, a later study demonstrated that K ATP channels can undergo constitutive endocytosis in the absence of PKC stimulation using a tyrosine-based endocytic signal located on the Kir6.2 subunit (17).…”

mentioning

confidence: 99%

Constitutive Endocytic Recycling and Protein Kinase C-mediated Lysosomal Degradation Control KATP Channel Surface Density

Manna¹,

Smith²,

Taneja

et al. 2010

Journal of Biological Chemistry

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Pancreatic ATP-sensitive potassium (K ATP ) channels control insulin secretion by coupling the excitability of the pancreatic ␤-cell to glucose metabolism. Little is currently known about how the plasma membrane density of these channels is regulated. We therefore set out to examine in detail the endocytosis and recycling of these channels and how these processes are regulated. To achieve this goal, we expressed K ATP channels bearing an extracellular hemagglutinin epitope in human embryonic kidney cells and followed their fate along the endocytic pathway. Our results show that K ATP channels undergo multiple rounds of endocytosis and recycling. Further, activation of protein kinase C (PKC) with phorbol 12-myristate 13-acetate significantly decreases K ATP channel surface density by reducing channel recycling and diverting the channel to lysosomal degradation. These findings were recapitulated in the model pancreatic ␤-cell line INS1e, where activation of PKC leads to a decrease in the surface density of native K ATP channels. Because sorting of internalized channels between lysosomal and recycling pathways could have opposite effects on the excitability of pancreatic ␤-cells, we propose that PKC-regulated K ATP channel trafficking may play a role in the regulation of insulin secretion.The ATP-sensitive potassium (K ATP ) channel plays a key role in the regulation of glucose-induced insulin secretion by the pancreatic ␤-cells (1-3). Central to this role is its unique ability to couple changes in the metabolism of glucose to changes in membrane potential. A rise in blood glucose levels increases the uptake and metabolism of glucose, resulting in an increase in the intracellular [ATP]/[ADP] ratio and inhibition of K ATP channels. This leads to depolarization of the ␤-cell membrane (caused by inhibition of K ϩ efflux), stimulating opening of voltage-activated calcium channels, Ca 2ϩ influx, and insulin release (4). Regulation of K ATP channel function by products of metabolism (e.g. nucleotides) as well as other cellular signals (e.g. protein kinases, lipids) has been extensively studied (1,5,6). By comparison, little is known about how the number of channels at the plasma membrane of the cell is controlled, although there is growing evidence that changes in the membrane density of the channel underlie disease states (7,8).Structurally, K ATP channels exist as octamers formed from four subunits of the inwardly rectifying potassium channel Kir6.1 or Kir6.2, together with four sulfonylurea receptor (SUR1, SUR2A, or SUR2B) subunits (5, 9 -11). The pancreatic K ATP channel comprises Kir6.2 and SUR1 subunits, which are encoded by the genes KCNJ11 and ABCC8, respectively (5, 6, 10, 11). Mutations in both of these genes are associated with disorders of insulin secretion including congenital hyperinsulinism and neonatal diabetes (4, 7). Studies have shown that although some mutations affect the nucleotide regulation of the channel (12-14), others alter the density of the channels at the cell surface by affecting traffickin...

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ATP-Sensitive Potassium Channel Traffic Regulation by Adenosine and Protein Kinase C

Cited by 109 publications

References 85 publications

Regulation of Cardiac ATP-sensitive Potassium Channel Surface Expression by Calcium/Calmodulin-dependent Protein Kinase II

Regulation of Cardiac ATP-sensitive Potassium Channel Surface Expression by Calcium/Calmodulin-dependent Protein Kinase II

ATP-sensitive K channel channel/enzyme multimer: Metabolic gating in the heart

Constitutive Endocytic Recycling and Protein Kinase C-mediated Lysosomal Degradation Control KATP Channel Surface Density

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