Drug-induced ion channel trafficking disturbance can cause cardiac arrhythmias. The subcellular level at which drugs interfere in trafficking pathways is largely unknown. KIR 2.1 inward rectifier channels, largely responsible for the cardiac inward rectifier current (IK1 ), are degraded in lysosomes. Amiodarone and dronedarone are class III antiarrhythmics. Chronic use of amiodarone, and to a l...

The inhibitory receptors for MHC class I have a central role in controlling natural killer (NK) cell activity. Soon after their discovery, it was found that these receptors have a degree of peptide selectivity. Such peptide selectivity has been demonstrated for all inhibitory killer cell immunoglobulin-like receptor (KIR) tested to date, certain activating KIR, and also members of the C-type le...

BACKGROUND Natural killer (NK) cells express killer immunoglobulin-like (KIR) inhibitory receptors, which recognize certain HLA class I molecules (KIR ligands), and stimulatory receptors such as FcgammaRIII. The purpose of this study was to test the possible influence of inhibitory KIR signaling on antibody-dependent cell cytotoxicity (ADCC) mediated by allogeneic NK cells against breast cancer...

Interactions between killer immunoglobulin-like receptors (KIRs) and their HLA-A, -B, and -C ligands diversify the functions of human natural killer cells. Consequently, combinations of KIR and HLA genotypes affect resistance to infection and autoimmunity, success of reproduction and outcome of hematopoietic cell transplantation. HLA-C, with its C1 and C2 epitopes, evolved in hominids to be spe...

Introduction: Tuberculosis (TB), caused by Mycobacterium Tuberculosis (Mtb), with more than nine million new cases and almost two million deaths in each year is a worldwide important public health problem. Generally, human immune responses prevent Mtb spread, and the infection remains in a latent state. Both, innate and adaptive immune responses are involved against TB. However, the role of the...

The defining structural feature of inward-rectifier potassium (Kir) channels is the unique Kir cytoplasmic domain. Recently we showed that salt bridges located at the cytoplasmic domain subunit interfaces (CD-Is) of eukaryotic Kir channels control channel gating via stability of a novel inactivated closed state. The cytoplasmic domains of prokaryotic and eukaryotic Kir channels show similar con...

The KIR genes and their HLA class I ligands have thus far not been investigated in pemphigus foliaceus (PF) and related autoimmune diseases, such as pemphigus vulgaris. We genotyped 233 patients and 204 controls for KIR by PCR-SSP. HLA typing was performed by LABType SSO reagent kits. We estimated the odds ratio, 95% confidence interval and performed logistic regression analyses to test the hyp...

OBJECTIVE To explore genes of the killer-cell immunoglobulin-like receptor (KIR) and of the HLA ligand and their relationship with the outcome of metastatic colorectal cancer (mCRC) patients treated with first-line 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI). METHODS A total of 224 mCRC patients were screened for KIR/HLA typing. The determination of the KIR/HLA combinations was based...

The inwardly rectifying K+ (Kir) current in mammalian retinal pigment epithelial (RPE) cells, which is largely mediated by Kir7.1 channels, is stable in cells dialyzed with MgATP but runs down when intracellular ATP is depleted. A potential mechanism for this rundown is a decrease in phosphatidylinositol 4,5-bisphosphate (PIP2) regeneration by ATP-dependent lipid kinases. Here, we used the whol...

Astrocytic inwardly rectifying K(+) currents (I(KIR)) have an important role in extracellular K(+) homeostasis, which influences neuronal excitability, and serum extravasation has been linked to impaired K(IR)-mediated K(+) buffering and chronic hyperexcitability. Head injury induces acute impairment in astroglial membrane I(KIR) and impaired K(+) buffering in the rat hippocampus, but chronic s...