Anionic Phospholipids Activate ATP-sensitive Potassium Channels

Fan, Zheng; Makielski, Jonathan C.

doi:10.1074/jbc.272.9.5388

Cited by 314 publications

(399 citation statements)

References 44 publications

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“…This has been demonstrated for PIP 2 direct regulation of several types of ion channels ( Fan and Makielski, 1997 ;Shyng et al, 2000 ;Suh and Hille, 2005 ;Roh á cs, 2007 ;Voets and Nilius, 2007 ). The critical dependence of BK channel activation on phosphoinositide ' s negative charges demonstrated here supports the hypothesis of a protein recognition site being involved.…”

Section: Pip 2 Direct Mechanism: Molecular Playerssupporting

confidence: 68%

“…In particular, PIP 2 directly modulates the activity of ion channels and transporters ( Hilgemann and Ball, 1996 ;Fan and Makielski, 1997 ;Runnels et al, 2002 ;Roh á cs et al, 2003 ;Chemin et al, 2005 ;Suh and Hille 2005 ;Brauchi et al, 2007 ;Hilgemann, 2007 ;Roh á cs 2007 ;Voets and Nilius, 2007 ). In spite of the key roles of PIP 2 and BK channels in cell excitability and signaling, it remains unknown whether PIP 2 can directly modulate BK channel function.…”

Section: Excised Patch Recordings From Vascular Myocytesmentioning

confidence: 99%

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Direct Regulation of BK Channels by Phosphatidylinositol 4,5-Bisphosphate as a Novel Signaling Pathway

Vaithianathan¹,

Bukiya²,

Liu³

et al. 2008

J Cell Biol

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Section: Pip 2 Direct Mechanism: Molecular Playerssupporting

confidence: 68%

Section: Excised Patch Recordings From Vascular Myocytesmentioning

confidence: 99%

Direct Regulation of BK Channels by Phosphatidylinositol 4,5-Bisphosphate as a Novel Signaling Pathway

Vaithianathan¹,

Bukiya²,

Liu³

et al. 2008

J Cell Biol

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“…Emerging evidence have indicated a novel mechanism for regulation of inward rectifying K ϩ channels via direct interaction with membrane phospholipids, PIP 2 (5,30,31). This direct interaction occurs between PIP 2 and several positively charged residues in the proximal C termini of the channel (5) and likely regulates channel opening by stabilizing the structure of the cytoplasmic entrance of the pore.…”

Section: Fig 6 Pkc Sensitivity Of Girk Channels Depends On Channel-mentioning

confidence: 99%

Mechanosensitivity of GIRK Channels Is Mediated by Protein Kinase C-dependent Channel-Phosphatidylinositol 4,5-Bisphosphate Interaction

Zhang

Lee

John

et al. 2004

Journal of Biological Chemistry

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Gprotein-activated inwardly rectifying K ؉ channel (GIRK or Kir3) currents are inhibited by mechanical stretch of the cell membrane, but the underlying mechanisms are not understood. In Xenopus oocytes heterologously expressing GIRK channels, membrane stretch induced by 50% reduction of osmotic pressure caused a prompt reduction of GIRK1/4, GIRK1, and GIRK4 currents by 16.6 -42.6%. Comparable GIRK current reduction was produced by protein kinase C (PKC) activation (phorbol 12-myristate 13-acetate). The mechanosensitivity of the GIRK4 current was abolished by pretreatment with PKC inhibitors (staurosporine or calphostin C). Neither hypo-osmotic challenge nor PKC activation affected IRK1 currents. GIRK4 chimera (GIRK4-IRK1-(Lys 207 -Leu 245 )) and single point mutant (GIRK4(I229L)), in which the phosphatidylinositol 4,5-bisphosphate (PIP 2 ) binding domain or residue was replaced by the corresponding region of IRK1 to strengthen the channel-PIP 2 interaction, showed no mechanosensitivity and minimal PKC sensitivity. IRK1 gained mechanosensitivity and PKC sensitivity by reverse double point mutation of the PIP 2 binding domain (L222I/R213Q). Overexpression of G␤␥, which is known to strengthen the channel-PIP 2 interaction, attenuated the mechanosensitivity of GIRK4 channels. In oocytes expressing a pleckstrin homology domain of PLC-␦ tagged with green fluorescent protein, hypo-osmotic challenge or PKC activation caused a translocation of the fluorescence signal from the cell membrane to the cytosol, reflecting PIP 2 hydrolysis. The translocation was prevented by pretreatment with PKC inhibitors. Involvement of PKC activation in the mechanosensitivity of muscarinic K ؉ channels was confirmed in native rabbit atrial myocytes. These results suggest that the mechanosensitivity of GIRK channels is mediated primarily by channel-PIP 2 interaction, with PKC playing an important role in modulating the interaction probably through PIP 2 hydrolysis.Muscarinic K ϩ (K ACh ) 1 channels in the heart are heterotetrameric channels composed of two subunits, GIRK1 (Kir3.1) and GIRK4 (Kir3.4) (1). The K ACh channels are stimulated by M 2 receptor activation in response to parasympathetic stimulation, which leads to the hyperpolarization of the membrane potential and results in a decreased heart rate (2, 3). In addition to this canonical activating pathway, molecules such as G␤␥, intracellular Na ϩ , and Mg 2ϩ also activate the GIRK channels by strengthening the phosphatidylinositol 4,5-bisphosphate (PIP 2 ) interaction with the channels (4). PIP 2 has been shown to directly interact with the C terminus of the GIRK channels and activate the channels as a membrane-delimited second messenger (5). GIRK channels have also been shown to be modulated by other factors such as mechanical stretch (6) and protein kinase C (PKC) (3, 7), although an involvement of PIP 2 is not known.Mechanical stimuli alter the electrophysiological properties of the heart. This mechanoelectrical feedback plays important roles in regulating cardiac function (8, 9)....

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“…The stimulatory effect seems to be confined to long-chain acyl-CoA esters, since addition of malonyl-CoA (3 carbon chain length) is without effect on the K ATP channel [8]. Unlike another recently described group of lipid activators, anionic phospholipids [11,12], LC-CoA esters seem to be highly specific for the K ATP channel [8,13]. The LC-CoA esters are, on a molar basis, 100 to 1000 times more potent than ADP [9] and both saturated and unsaturated LCCoA esters induce a rapid, reversible activation of the beta-cell K ATP channel [8].…”

mentioning

confidence: 99%

Long-Chain CoA esters activate human pancreatic beta-cell K ATP channels: potential role in Type 2 diabetes

et al. 2004

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Aims/hypothesis. The ATP-regulated potassium (K ATP ) channel in the pancreatic beta cell couples the metabolic state to electrical activity. The primary regulator of the K ATP channel is generally accepted to be changes in ATP/ADP ratio, where ATP inhibits and ADP activates channel activity. Recently, we showed that long-chain CoA (LC-CoA) esters form a new class of potent K ATP channel activators in rodents, as studied in inside-out patches. Methods. In this study we have investigated the effects of LC-CoA esters in human pancreatic beta cells using the inside-out and whole-cell configurations of the patch clamp technique. Results. Human K ATP channels were potently activated by acyl-CoA esters with a chain length exceeding 12 carbons. Activation by LC-CoA esters did not require the presence of Mg 2+ or adenine nucleotides. A detailed characterization of the concentration-dependent relationship showed an EC 50 of 0.7±0.1 µmol/l. Furthermore, in the presence of an ATP/ADP ratio of 10 (1.1 mmol/l total adenine nucleotides), whole-cell K ATP channel currents increased approximately sixfold following addition of 1 µmol/l LC-CoA ester. The presence of 1 µmol/l LC-CoA in the recording pipette solution increased beta-cell input conductance, from 0.5±0.2 nS to 2.5±1.3 nS. Conclusion/interpretation. Taken together, these results show that LC-CoA esters are potent activators of the K ATP channel in human pancreatic beta cells. The fact that LC-CoA esters also stimulate K ATP channel activity recorded in the whole-cell configuration, points to the ability of these compounds to have an important modulatory role of human beta-cell electrical activity under both physiological and pathophysiological conditions. [Diabetologia (2004) essential function has been included in the model of glucose-induced insulin secretion. In this model, increases in blood glucose levels lead to metabolism of glucose which generates an increase in the ATP/ADP ratio. The consensus view is that increases in the ATP/ADP ratio promote closure of the beta-cell K ATP channel, thereby depolarizing the cell membrane resulting in opening of voltage-dependent Ca 2+ channels. The subsequent rise in cytoplasmic free Ca 2+ concentration triggers a series of events leading to exocytosis of insulin. Hence, the K ATP channel provides a critical link between glucose metabolism, electrical activity and insulin secretion in the pancreatic beta cell.The most important molecular regulators of K ATP channel activity are believed to be adenine nucleo-ATP-sensitive potassium (K ATP ) channels play a key role in the coupling between cellular metabolism and electrical activity in a wide range of tissues. Since the discovery of these channels in the beta cell [1], their

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Anionic Phospholipids Activate ATP-sensitive Potassium Channels

Cited by 314 publications

References 44 publications

Direct Regulation of BK Channels by Phosphatidylinositol 4,5-Bisphosphate as a Novel Signaling Pathway

Direct Regulation of BK Channels by Phosphatidylinositol 4,5-Bisphosphate as a Novel Signaling Pathway

Mechanosensitivity of GIRK Channels Is Mediated by Protein Kinase C-dependent Channel-Phosphatidylinositol 4,5-Bisphosphate Interaction

Long-Chain CoA esters activate human pancreatic beta-cell K ATP channels: potential role in Type 2 diabetes

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