OBJECTIVETo diagnose a Chinese benign familial neonatal convulsions (BFNC) family at the level of gene and investigate its molecular pathogenesis.

METHODSAll family members were studied by clinical examinations and linkage analysis. Mutation analysis of KCNQ2 gene was made by means of polymerase chain reaction (PCR)-direct sequencing and PCR-single strand conformation polymorphism (SSCP) in the proband, 16 family members and 72 unrelated normal individuals.

RESULTSLinkage analysis hinted the linkage of BFNC to KCNQ2, while the linkage to KCNQ3 was excluded. Mutation 1931delG of KCNQ2 gene was found in the proband by DNA-direct sequencing. The same SSCP variant as the proband's was showed in the rest affected members of this family but not in the unaffected members of this family and all of the 72 unrelated normal individuals.

CONCLUSION1931delG of KCNQ2 gene can cause BFNC in China and is novel mutation. The combination of linkage analysis and gene analysis is useful for gene diagnosis.

Epilepsy, Benign Neonatal ; genetics ; Female ; Genetic Linkage ; Humans ; Infant, Newborn ; KCNQ2 Potassium Channel ; KCNQ3 Potassium Channel ; Mutation ; Potassium Channels ; chemistry ; genetics ; Potassium Channels, Voltage-Gated

Epilepsy is one of the most common and debilitating neurological diseases that affects more than 40 million people worldwide. Genetic factors contribute to the pathogenesis of epilepsy. Molecular genetic studies have identified 15 disease-causing genes for epilepsy. The majority of the genes encode ion channels, including voltage-gated potassium channels KCNQ2 and KCNQ3, sodium channels SCN1A, SCN2A, and SCN1B, chloride channels CLCN2, and ligand-gated ion channels CHRNA4, CHRNB2, GABRG2, and GABRA1. Interestingly, non-ion channel genes have also been identified as epilepsy genes, and these genes include G-protein-coupled receptor MASS1/VLGR1, GM3 synthase, and proteins with unknown functions such as LGI1, NHLRC1, and EFHC1. These studies make genetic testing possible in some patients, and further characterization of the identified epilepsy genes may lead to the development of new drugs and new treatments for patients with epilepsy.
Chloride Channels ; genetics ; Epilepsies, Myoclonic ; genetics ; Epilepsy ; genetics ; Epilepsy, Absence ; genetics ; Humans ; KCNQ2 Potassium Channel ; genetics ; KCNQ3 Potassium Channel ; genetics ; NAV1.1 Voltage-Gated Sodium Channel ; NAV1.2 Voltage-Gated Sodium Channel ; Nerve Tissue Proteins ; genetics ; Sodium Channels ; genetics

The long QT syndrome (LQTS) is a rare hereditary disorder in which affected individuals have a possibility of ventricular tachyarrhythmia and sudden cardiac death. We investigated 62 LQTS (QTc > or = 0.47 sec) and 19 family members whose genetic study revealed mutation of LQT gene. In the proband group, the modes of presentation were ECG abnormality (38.7%), aborted cardiac arrest (24.2%), and syncope or seizure (19.4%). Median age of initial symptom development was 10.5 yr. Genetic studies were performed in 61; and mutations were found in 40 cases (KCNQ1 in 19, KCNH2 in 10, SCN5A in 7, KCNJ2 in 3, and CACNA1C in 1). In the family group, the penetrance of LQT gene mutation was 57.9%. QTc was longer as patients had the history of syncope (P = 0.001), ventricular tachycardia (P = 0.017) and aborted arrest (P = 0.010). QTc longer than 0.508 sec could be a cut-off value for major cardiac events (sensitivity 0.806, specificity 0.600). Beta-blocker was frequently applied for treatment and had significant effects on reducing QTc (P = 0.007). Implantable cardioverter defibrillators were applied in 6 patients. Congenital LQTS is a potentially lethal disease. It shows various genetic mutations with low penetrance in Korean patients.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group/genetics ; Calcium Channels/genetics ; Child ; Child, Preschool ; Electrocardiography ; Heart Arrest/genetics/pathology ; Humans ; Infant ; KCNQ1 Potassium Channel/genetics ; KCNQ2 Potassium Channel/genetics ; Long QT Syndrome/*diagnosis/*genetics ; Middle Aged ; Mutation/*genetics ; NAV1.5 Voltage-Gated Sodium Channel/genetics ; Penetrance ; Potassium Channels, Inwardly Rectifying/genetics ; Republic of Korea ; Risk Factors ; Seizures/genetics/pathology ; Young Adult

AIMTo study the mRNA expression changes in the brain of rats after middle cerebral artery occlusion.

METHODSMiddle cerebral artery occlusion was used to induce ischemia in rat brain. The mRNA expression of voltage-dependent potassium channel subtypes, including Kv1.4, Kv1.5, Kv2.1 and Kv4.2, were detected in rat hippocampus and cortex by RT-PCR.

RESULTSMiddle cerebral artery occlusion induced a significant neurological injury in rats. After ischemia 2 h, the mRNA of Kv1.4, Kv2.1 and Kv4.2 in hippocampus increased by 50%, 67% and 90% , respectively. And the mRNA of Kv1.4 and Kv4.2 maintained at a high level in hippocampus after ischemia 24 h. In cortex, the mRNA level of all the four subtypes were not changed significantly after ischemia 2 h, but the mRNA of Kv2.1 and Kv4.2 increased by 70% and 62% after ischemia 24 h, respectively.

CONCLUSIONThe mRNA expression levels of voltage-dependent potassium channels were up-regulated in rat hippocampus and cortex after middle cerebral artery occlusion.

Animals ; Brain ; metabolism ; Infarction, Middle Cerebral Artery ; metabolism ; Kv1.4 Potassium Channel ; biosynthesis ; genetics ; Kv1.5 Potassium Channel ; biosynthesis ; genetics ; Male ; Potassium Channels, Voltage-Gated ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Wistar ; Shab Potassium Channels ; biosynthesis ; genetics ; Shal Potassium Channels ; biosynthesis ; genetics ; Up-Regulation

To investigate the role of potassium channels in the pathogenesis of airway hyperresponsiveness induced by cigarette smoking, the alteration in expression of large-conductance calcium-activated potassium channel (BKca) and voltage-dependent delayed rectifier potassium channel (Kv1.5) in bronchial smooth muscle cells were investigated in chronic cigarette smoking rats. Airway responsiveness was determined, hematoxylin and eosin staining, immuno-histochemistry, in-situ hybridization and western blot techniques were used. The results showed: (1) Chronic cigarette smoking down-regulated the protein synthesis and mRNA expression of BKca and Kv1.5 in bronchial and bronchiolar smooth muscles. (2) BKca decreased more markedly than Kv1.5 in bronchi, but there was no difference between them in bronchioli. (3) No changes in the expression of these two potassium channel proteins were found in extracted cell membrane protein from lung tissue. The results suggest that chronic cigarette smoking can down-regulate the levels of BKca and Kv1.5 in rat bronchial smooth muscle cells in vivo, which might contribute to the mechanism of airway hyperresponsiveness induced by cigarette smoking.
Animals ; Bronchi ; metabolism ; Cells, Cultured ; Kv1.5 Potassium Channel ; Male ; Muscle, Smooth ; cytology ; metabolism ; Potassium Channels, Calcium-Activated ; biosynthesis ; genetics ; Potassium Channels, Voltage-Gated ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Sprague-Dawley ; Smoking ; adverse effects

Humans ; Potassium Channels, Inwardly Rectifying ; chemistry ; classification ; physiology ; Potassium Channels, Tandem Pore Domain ; chemistry ; classification ; physiology ; Protein Structure, Tertiary

Epilepsy is a group of disorders characterized by recurrent seizures. The etiologies of idiopathic epilepsy commonly have a genetic basis. Gene mutations causing several of the inherited epilepsies have been mapped. In this review, the authors summarize the available information on the genetic basis of human epilepsies and epilepsy syndromes, emphasizing how genetic defects may correlate with the pathophysiological mechanisms of brain hyperexcitability and gene defects can lead to epilepsy by altering multiple and diverse aspects of neuronal function.
Epilepsy ; genetics ; Humans ; KCNQ2 Potassium Channel ; Mutation ; NAV1.1 Voltage-Gated Sodium Channel ; Nerve Tissue Proteins ; genetics ; Potassium Channels ; genetics ; Potassium Channels, Voltage-Gated ; Receptors, Nicotinic ; genetics ; Research ; trends ; Research Design ; Sodium Channels ; genetics ; Voltage-Gated Sodium Channel beta-1 Subunit

G protein-coupled inward rectifier K(+) channel 4(GIRK4) is a G protein-coupled inward rectifier potassium channel family member. Encoded by the KCNJ5, it is widely distributed in the mammalian heart, brain, and other tissues and organs. Recent studies have demonstrated that the abnormal expression of GIRK4 gene is associated with atrial fibrillation, and meanwhile may be closely related to obesity, metabolic syndrome, and many other clinical conditions. Further research on the role the GIRK4 gene in the pathophysiology of these clinical conditions will definitely facilitate their clinical diagnosis and treatment.
Atrial Fibrillation ; genetics ; G Protein-Coupled Inwardly-Rectifying Potassium Channels ; genetics ; Humans ; Metabolic Syndrome ; genetics

OBJECTIVETo investigate the effect of diclofenac on the expression of Kv1.3 and Kir2.1 channels in human macrophages and the membrane potential and foaming process of the macrophages.

METHODSThe effect of diclofenac on the expression of Kv1.3 and Kir2.1 channels in cultured human monocyte-derived macrophages was investigated using real-time RT-PCR and Western blotting, and its effect on the membrane potential was analyzed with optical mapping of the membrane potential with voltage-sensitive dyes. The ratio of cholesterol ester (CE) in the macrophages following intake of oxidized low-density lipoprotein (OxLDL) was analyzed by an enzymatic fluorometric method.

RESULTSThe expression of Kv1.3 and Kir2.1 channels in the macrophages were down-regulated by diclofenac (1.5 µmol/L and 15 µmol/L). Compared with those in the control group, Kv1.3 mRNA expression was reduced by over 80% and 90% (P<0.05), and Kir2.1 mRNA by over 20% and 30% (P>0.05), respectively; both their protein expression was reduced by over 10% and 60% with a dose- dependent effect (P<0.05). Diclofenac at the two doses dose-dependently reduced the surface fluorescence intensity of the macrophage, and the membrane potential was decreased by 28% and 54%, respectively (P<0.05). Incubation of the macrophages with 30 mg/L OxLDL for 60 h caused an obvious enlargement of the cell volume and deposition of numerous lipid granules in cytoplasm, resulting also in a CE/TC ratio over 50% (P<0.05). Diclofenac at 1.5 and 15 µmol/L both significantly decreased the CE/TC ratio to (23.624∓3.34)% and (13.601∓2.916)% (P<0.05), respectively, but this effect did not show a dose-response relationship (P>0.05).

CONCLUSIONDiclofenac can significant down-regulate the expression of Kv1.3 and Kir2.1 channels in human macrophages, lower their membrane potential and inhibit the process of foam cell formation.

Cells, Cultured ; Diclofenac ; pharmacology ; Foam Cells ; cytology ; drug effects ; Humans ; Kv1.3 Potassium Channel ; metabolism ; Macrophages ; drug effects ; metabolism ; physiology ; Membrane Potentials ; drug effects ; Potassium Channels, Inwardly Rectifying ; metabolism

Animals ; Asthma ; physiopathology ; Bronchi ; metabolism ; Bronchial Hyperreactivity ; etiology ; Humans ; Muscle, Smooth ; metabolism ; Potassium Channels ; chemistry ; physiology ; Potassium Channels, Calcium-Activated ; physiology ; Potassium Channels, Voltage-Gated ; physiology