Severe Lactational Mastitis With Complicated Wound Infection Caused by .

Introduction: Puerperal mastitis, a complication occurring during the breastfeeding period, is often caused by . Here we report on severe mastitis in a lactating breast, with subsequent invasive disease and wound healing problems.

Main Issue: The 41-year-old woman (G2, P2) presented at 2 weeks postpartum to our hospital with painful swelling and reddening of the left breast, in addition to fever and malaise, and complained about a nipple fissure on the left breast.

The Phosphodiesterase Inhibitor IBMX Blocks the Potassium Channel THIK-1 from the Extracellular Side.

The two-pore domain potassium channel (K-channel) THIK-1 has several predicted protein kinase A (PKA) phosphorylation sites. In trying to elucidate whether THIK-1 is regulated via PKA, we expressed THIK-1 channels in a mammalian cell line (CHO cells) and used the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX) as a pharmacological tool to induce activation of PKA. Using the whole-cell patch-clamp recording, we found that THIK-1 currents were inhibited by application of IBMX with an IC of 120 µM.

Do we need a 200 μg misoprostol vaginal insert? A retrospective cohort study comparing the misoprostol vaginal insert to oral misoprostol.

Aim: The misoprostol vaginal insert (MVI) was reported to be more effective than dinoprostone but discussed critically because of high rates of fetal heart rate changes due to uterine tachysystole. The aim of this study was to investigate the outcome of induced labor using the MVI compared to off-label orally-administered misoprostol (OM).

Methods: Retrospective study including a total of 401 patients with singleton pregnancies in whom labor was induced at ≥36 0/7 gestational weeks with MVI (203) or OM (198).

Much more than a leak: structure and function of K₂p-channels.

Over the last decade, we have seen an enormous increase in the number of experimental studies on two-pore-domain potassium channels (K2P-channels). The collection of reviews and original articles compiled for this special issue of Pflügers Archiv aims to give an up-to-date summary of what is known about the physiology and pathophysiology of K2P-channels. This introductory overview briefly describes the structure of K2P-channels and their function in different organs.

The role of protein-protein interactions in the intracellular traffic of the potassium channels TASK-1 and TASK-3.

The intracellular transport of membrane proteins is controlled by trafficking signals: Short peptide motifs that mediate the contact with COPI, COPII or various clathrin-associated coat proteins. In addition, many membrane proteins interact with accessory proteins that are involved in the sorting of these proteins to different intracellular compartments. In the K2P channels, TASK-1 and TASK-3, the influence of protein-protein interactions on sorting decisions has been studied in some detail.

The potassium current carried by TREK-1 channels in rat cardiac ventricular muscle.

We studied the potassium current flowing through TREK-1 channels in rat cardiac ventricular myocytes. We separated the TREK-1 current from other current components by blocking most other channels with a blocker cocktail. We tried to inhibit the TREK-1 current by activating protein kinase A (PKA) with a mixture of forskolin and isobutyl-methylxanthine (IBMX).

Cooperative endocytosis of the endosomal SNARE protein syntaxin-8 and the potassium channel TASK-1.

The endosomal SNARE protein syntaxin-8 interacts with the acid-sensitive potassium channel TASK-1. The functional relevance of this interaction was studied by heterologous expression of these proteins (and mutants thereof) in Xenopus oocytes and in mammalian cell lines. Coexpression of syntaxin-8 caused a fourfold reduction in TASK-1 current, a corresponding reduction in the expression of TASK-1 at the cell surface, and a marked increase in the rate of endocytosis of the channel.

Breaking the silence: functional expression of the two-pore-domain potassium channel THIK-2.

THIK-2 belongs to the 'silent' channels of the two-pore-domain potassium channel family. It is highly expressed in many nuclei of the brain but has so far resisted all attempts at functional expression. THIK-2 has a highly conserved 19-amino-acid region in its N terminus (residues 6-24 in the rat orthologue) that is missing in the closely related channel THIK-1.

A splice variant of the two-pore domain potassium channel TREK-1 with only one pore domain reduces the surface expression of full-length TREK-1 channels.

We have identified a novel splice variant of the human and rat two-pore domain potassium (K2P) channel TREK-1. The splice variant TREK-1e results from skipping of exon 5, which causes a frame shift in exon 6. The frame shift produces a novel C-terminal amino acid sequence and a premature termination of translation, which leads to a loss of transmembrane domains M3 and M4 and of the second pore domain.

A semisynthetic fusicoccane stabilizes a protein-protein interaction and enhances the expression of K+ channels at the cell surface.

Small-molecule stabilization of protein-protein interactions is an emerging field in chemical biology. We show how fusicoccanes, originally identified as fungal toxins acting on plants, promote the interaction of 14-3-3 proteins with the human potassium channel TASK-3 and present a semisynthetic fusicoccane derivative (FC-THF) that targets the 14-3-3 recognition motif (mode 3) in TASK-3. In the presence of FC-THF, the binding of 14-3-3 proteins to TASK-3 was increased 19-fold and protein crystallography provided the atomic details of the effects of FC-THF on this interaction.

The inhibition of the potassium channel TASK-1 in rat cardiac muscle by endothelin-1 is mediated by phospholipase C.

Aims: The two-pore-domain potassium channel TASK-1 is robustly inhibited by the activation of receptors coupled to the Gα(q) subgroup of G-proteins, but the signal transduction pathway is still unclear. We have studied the mechanisms by which endothelin receptors inhibit the current carried by TASK-1 channels (I(TASK)) in cardiomyocytes.

Methods And Results: Patch-clamp measurements were carried out in isolated rat cardiomyocytes.

The glycolytic enzymes glyceraldehyde 3-phosphate dehydrogenase and enolase interact with the renal epithelial K+ channel ROMK2 and regulate its function.

Background/aims: ROMK channels mediate potassium secretion and regulate NaCl reabsorption in the kidney. The aim was to study the functional implications of the interaction between ROMK2 (Kir1.1b) and two glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and enolase-α, which were identified as potential regulatory subunits of the channel complex.

TASK-1 channels may modulate action potential duration of human atrial cardiomyocytes.

Background/aims: Atrial fibrillation is the most common arrhythmia in the elderly, and potassium channels with atrium-specific expression have been discussed as targets to treat atrial fibrillation. Our aim was to characterize TASK-1 channels in human heart and to functionally describe the role of the atrial whole cell current I(TASK-1).

Methods And Results: Using quantitative PCR, we show that TASK-1 is predominantly expressed in the atria, auricles and atrio-ventricular node of the human heart.

Altered stress stimulation of inward rectifier potassium channels in Andersen-Tawil syndrome.

Inward rectifier potassium channels of the Kir2 subfamily are important determinants of the electrical activity of brain and muscle cells. Genetic mutations in Kir2.1 associate with Andersen-Tawil syndrome (ATS), a familial disorder leading to stress-triggered periodic paralysis and ventricular arrhythmia.

Knock-out of the potassium channel TASK-1 leads to a prolonged QT interval and a disturbed QRS complex.

Background/aims: The aim of the study was to characterize the whole cell current of the two-pore domain potassium channel TASK-1 (K2P3) in mouse ventricular cardiomyocytes (I(TASK-1)) and to analyze the cardiac phenotype of the TASK-1(-/-) mice.

Methods And Results: We have quantified the ventricular I(TASK-1) current using the blocker A293 and TASK-1(-/-) mice. Surface electrocardiogram recordings of TASK-1(-/-) mice showed a prolonged QTc interval and a broadened QRS complex.

Membrane proteins as 14-3-3 clients in functional regulation and intracellular transport.

14-3-3 proteins regulate the function and subcellular sorting of membrane proteins. Often, 14-3-3 binding to client proteins requires phosphorylation of the client, but the relevant kinase is unknown in most cases. We summarize current progress in identifying kinases that target membrane proteins with 14-3-3 binding sites and discuss the molecular mechanisms of 14-3-3 action.

A specific two-pore domain potassium channel blocker defines the structure of the TASK-1 open pore.

Two-pore domain potassium (K(2P)) channels play a key role in setting the membrane potential of excitable cells. Despite their role as putative targets for drugs and general anesthetics, little is known about the structure and the drug binding site of K(2P) channels. We describe A1899 as a potent and highly selective blocker of the K(2P) channel TASK-1.

Calcium-activated K(+) channel (K(Ca)3.1) activity during Ca(2+) store depletion and store-operated Ca(2+) entry in human macrophages.

STIM1 'senses' decreases in endoplasmic reticular (ER) luminal Ca(2+) and induces store-operated Ca(2+) (SOC) entry through plasma membrane Orai channels. The Ca(2+)/calmodulin-activated K(+) channel K(Ca)3.1 (previously known as SK4) has been implicated as an 'amplifier' of the Ca(2+)-release activated Ca(2+) (CRAC) current, especially in T lymphocytes.

RNA editing modulates the binding of drugs and highly unsaturated fatty acids to the open pore of Kv potassium channels.

The time course of inactivation of voltage-activated potassium (Kv) channels is an important determinant of the firing rate of neurons. In many Kv channels highly unsaturated lipids as arachidonic acid, docosahexaenoic acid and anandamide can induce fast inactivation. We found that these lipids interact with hydrophobic residues lining the inner cavity of the pore.

5-Hydroxydecanoate and coenzyme A are inhibitors of native sarcolemmal KATP channels in inside-out patches.

Background: 5-Hydroxydecanoate (5-HD) inhibits preconditioning, and it is assumed to be a selective inhibitor of mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channels. However, 5-HD is a substrate for mitochondrial outer membrane acyl-CoA synthetase, which catalyzes the reaction: 5HD + CoA + ATP --> 5-HD-CoA (5-hydroxydecanoyl-CoA) + AMP + pyrophosphate. We aimed to determine whether the reactants or principal product of this reaction modulate sarcolemmal K(ATP) (sarcK(ATP)) channel activity.

Intracellular traffic of the K+ channels TASK-1 and TASK-3: role of N- and C-terminal sorting signals and interaction with 14-3-3 proteins.

The two-pore-domain potassium channels TASK-1 (KCNK3) and TASK-3 (KCNK9) modulate the electrical activity of neurons and many other cell types. We expressed TASK-1, TASK-3 and related reporter constructs in Xenopus oocytes, mammalian cell lines and various yeast strains to study the mechanisms controlling their transport to the surface membrane and the role of 14-3-3 proteins. We measured potassium currents with the voltage-clamp technique and fused N- and C-terminal fragments of the channels to various reporter proteins to study changes in subcellular localisation and surface expression.

Mutation of histidine 105 in the T1 domain of the potassium channel Kv2.1 disrupts heteromerization with Kv6.3 and Kv6.4.

The voltage-activated K(+) channel subunit Kv2.1 can form heterotetramers with members of the Kv6 subfamily, generating channels with biophysical properties different from homomeric Kv2.1 channels.

Structural determinants of Kvbeta1.3-induced channel inactivation: a hairpin modulated by PIP2.

Inactivation of voltage-gated Kv1 channels can be altered by Kvbeta subunits, which block the ion-conducting pore to induce a rapid ('N-type') inactivation. Here, we investigate the mechanisms and structural basis of Kvbeta1.3 interaction with the pore domain of Kv1.