Physical and emotional stress is accompanied by release of stress hormones such as the glucocorticoid cortisol. This hormone upregulates the serumand glucocorticoid-inducible kinase (SGK)1, which in turn stimulates IKs, a slow delayed rectifier potassium current that mediates cardiac action potential repolarization. Mutations in IKs channel (KCNQ1, KvLQT1, Kv7.1) or (KCNE1, IsK, minK) subunits ...

Physical and emotional stress is accompanied by release of stress hormones such as the glucocorticoid cortisol. This hormone upregulates the serum- and glucocorticoid-inducible kinase (SGK)1, which in turn stimulates I(Ks), a slow delayed rectifier potassium current that mediates cardiac action potential repolarization. Mutations in I(Ks) channel alpha (KCNQ1, KvLQT1, Kv7.1) or beta (KCNE1, IsK...

AIM Genome-wide association studies have identified >30 common variants associated with Type 2 diabetes (>5% minor allele frequency). These variants have small effects on individual risk and do not account for a large proportion of the heritable component of the disease. Monogenic forms of diabetes are caused by mutations that occur in <1:2000 individuals and follow strict patterns of inheritan...

Human Insulin Promoter Factor 1 (IPF-1) gene plays an important role in the embryonic development of pancreas and in the transcriptional regulation of insulin production. Mutations in this gene are known to cause pancreatic agenesis and diabetes mellitus. A detailed bioinformatic study of all the known mutations from HGMD database in the IPF-1 gene revealed interesting information. The informat...

Genetic and physiological studies have established a link between potassium channel dysfunction and a number of neurological and muscular disorders. Many 'channelopathies' are accounted for by a dominant-lethal suppression of potassium channel function. In the cardiac I(KS) channel complex comprising the alpha and beta subunits, KvLQT1 and IsK, respectively, several mutations lead to a dominant...

The long QT syndrome (LQTS) is a heritable disorder that predisposes to sudden cardiac death. LQTS is caused by mutations in ion channel genes including HERG and KCNE1, but the precise mechanisms remain unclear. To clarify this situation we injected adenoviral vectors expressing wild-type or LQT mutants of HERG and KCNE1 into guinea pig myocardium. End points at 48-72 h included electrophysiolo...

The KCNE1 gene product (minK protein) associates with the cardiac KvLQT1 potassium channel (encoded by KCNQ1) to create the cardiac slowly activating delayed rectifier, I(Ks). Mutations throughout both genes are linked to the hereditary cardiac arrhythmias in the Long QT Syndrome (LQTS). KCNE1 exerts its specific regulation of KCNQ1 activation via interactions between membrane-spanning segments...

IKs channels are voltage dependent and K+ selective. They influence cardiac action potential duration through their contribution to myocyte repolarization. Assembled from minK and KvLQT1 subunits, IKs channels are notable for a heteromeric ion conduction pathway in which both subunit types contribute to pore formation. This study was undertaken to assess the effects of minK on pore function. We...

Ferredoxin reductase (Fd-reductase) supplies electrons to mitochondrial steroid hydroxylase cytochrome P450 enzymes via a [2Fe-2S] ferredoxin. Chemical labeling studies with bovine Fd-reductase have implicated Lys-243 as important in binding to bovine ferredoxin (Hamamoto, I., Kazutaka, K., Tanaka, S., and Ichikawa, Y. (1988) Biochim. Biophys. Acta 953, 207-213). We have used site-directed muta...

The transcription factor insulin promoter factor-1 (IPF-1) plays a central role in both the development of the pancreas and the regulation of insulin gene expression in the mature pancreatic beta cell. A dominant-negative frameshift mutation in the IPF-l gene was identified in a single family and shown to cause pancreatic agenesis when homozygous and maturity-onset diabetes of the young (MODY) ...