Anionic Phospholipids Bind to and Modulate the Activity of Human TRESK Background K Channel.

The background K channel TRESK regulates sensory neuron excitability, and changes in its function/expression contribute to neuronal hyperexcitability after injury/inflammation, making it an attractive therapeutic target for pain-related disorders. Factors that change lipid bilayer composition/properties (including volatile anesthetics, chloroform, chlorpromazine, shear stress, and cell swelling/shrinkage) modify TRESK current, but despite the importance of anionic phospholipids (e.g.

Pyrethroids inhibit K2P channels and activate sensory neurons: basis of insecticide-induced paraesthesias.

Pyrethroid insecticides are widely used for pest control in agriculture or in human public health commonly as a topical treatment for scabies and head lice. Exposure to pyrethroids such as permethrin or tetramethrin (TM) causes sensory alterations such as transient pain, burning, stinging sensations, and paraesthesias. Despite the well-known effects of pyrethroids on sodium channels, actions on other channels that control sensory neuron excitability are less studied.

Ion Channels in the Eye: Involvement in Ocular Pathologies.

The eye is the sensory organ of vision. There, the retina transforms photons into electrical signals that are sent to higher brain areas to produce visual sensations. In the light path to the retina, different types of cells and tissues are involved in maintaining the transparency of avascular structures like the cornea or lens, while others, like the retinal pigment epithelium, have a critical role in the maintenance of photoreceptor function by regenerating the visual pigment.

Acid-sensing ion channels detect moderate acidifications to induce ocular pain.

Sensory nerve fibers innervating the ocular anterior surface detect external stimuli producing innocuous and painful sensations. Protons are among the first mediators released by damaged cells during inflammation, tissue injury, or other chronic ophthalmic conditions. We studied whether acid-sensing ion channels (ASICs) are expressed in corneal sensory neurons and their roles in the response to moderate acidifications of the ocular surface and in pathologies producing ocular surface inflammation.

Crosstalk between PI(4,5)P₂and CK2 modulates actin polymerization during endocytic uptake.

A transient burst of actin polymerization assists endocytic budding. How actin polymerization is controlled in this context is not understood. Here, we show that crosstalk between PI(4,5)P₂and the CK2 catalytic subunit Cka2 controls actin polymerization at endocytic sites.

Modulation of TRESK background K+ channel by membrane stretch.

The two-pore domain K(+) channel TRESK is expressed in dorsal root ganglion and trigeminal sensory neurons where it is a major contributor to background K(+) current. TRESK acts as a break to prevent excessive sensory neuron activation and decreases in its expression or function have been involved in neuronal hyperexcitability after injury/inflammation, migraine or altered sensory perception (tingling, cooling and pungent burning sensations). All these effects have implicated this channel in nociception and mechanotransduction.

Function and regulation of Saccharomyces cerevisiae myosins-I in endocytic budding.

Myosins-I are widely expressed actin-dependent motors which bear a phospholipid-binding domain. In addition, some members of the family can trigger Arp2/3 complex (actin-related protein 2/3 complex)-dependent actin polymerization. In the early 1990s, the development of powerful genetic tools in protozoa and mammals and discovery of these motors in yeast allowed the demonstration of their roles in membrane traffic along the endocytic and secretory pathways, in vacuole contraction, in cell motility and in mechanosensing.

Calmodulin dissociation regulates Myo5 recruitment and function at endocytic sites.

Myosins-I are conserved proteins that bear an N-terminal motor head followed by a Tail Homology 1 (TH1) lipid-binding domain. Some myosins-I have an additional C-terminal extension (C(ext)) that promotes Arp2/3 complex-dependent actin polymerization. The head and the tail are separated by a neck that binds calmodulin or calmodulin-related light chains.

Basal secretion of von Willebrand factor from human endothelial cells.

Endothelial cells store the adhesive glycoprotein von Willebrand factor (VWF) in Weibel-Palade bodies (WPBs), distinctively shaped regulated secretory organelles that undergo exocytosis in response to secretagogue. A significant proportion of newly synthesized VWF is also secreted spontaneously from nonstimulated cells, through what is thought to be the constitutive secretory pathway. To learn more about VWF trafficking, we performed kinetic analyses of the storage and nonstimulated secretion of VWF in cultured human endothelial cells.

Immunolocalization of KATP channel subunits in mouse and rat cardiac myocytes and the coronary vasculature.

Background: Electrophysiological data suggest that cardiac KATP channels consist of Kir6.2 and SUR2A subunits, but the distribution of these (and other KATP channel subunits) is poorly defined. We examined the localization of each of the KATP channel subunits in the mouse and rat heart.

Multisite phosphorylation mechanism for protein kinase A activation of the smooth muscle ATP-sensitive K+ channel.

The activation of ATP-sensitive K+ channels by protein kinase A in vascular smooth muscle is an important component of the action of vasodilators. In this study, we examine the molecular mechanisms of regulation of the cloned equivalent of this channel comprising the sulfonylurea receptor 2B and the inward rectifier 6.1 subunit (SUR2B/Kir6.

Do anionic phospholipids serve as cofactors or second messengers for the regulation of activity of cloned ATP-sensitive K+ channels?

The regulation of ion channels by anionic phospholipids is currently very topical. An outstanding issue is whether phosphatidylinositol 4,5-diphosphate and related species act as true second messengers in signaling or behave in a manner analogous to an enzymatic cofactor. This question is especially pertinent regarding ATP-sensitive K+ channels in smooth muscle, for which there is substantial literature supporting inhibitory regulation by hormones.

The cytoplasmic C-terminus of the sulfonylurea receptor is important for KATP channel function but is not key for complex assembly or trafficking.

ATP-sensitive K+ channels are an octameric assembly of two proteins, a sulfonylurea receptor (SUR1) and an ion conducting subunit (Kir 6.0). We have examined the role of the C-terminus of SUR1 by expressing a series of truncation mutants together with Kir6.

Assembly limits the pharmacological complexity of ATP-sensitive potassium channels.

ATP-sensitive potassium channels (K(ATP) channels) are formed from an octameric complex of an inwardly rectifying K(+) channel (Kir6.1, Kir6.2) and a sulfonylurea receptor (SUR1, SUR2A, and SUR2B).