Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chromanol 293B and dofetilide are inhibitors of IKs and IKr, i.e., of the slow and the rapid component of the delayed rectifier potassium current. The specificity of these drugs was tested by investigating their effects on the delayed rectifier potassium current in vascular smooth muscle, regulating the tone of blood vessels. Using depolarizing step protocols with asymmetrical potassium concentrations (135/4.5 mM K+ in pipette/bath), voltage-dependent K+ currents (IKv) of enzymatically dispersed guinea pig portal vein cells were studied in the whole-cell patch-clamp technique. Peak currents were obtained within 20 ms (at +50 mV) after activation. During a 10 s test pulse to +60 mV, these currents exhibited a relatively fast inactivation with time constants of 384 ms (Tfast) and 4505 ms (Tslow). Dofetilide was totally ineffective in modulating currents; in contrast, after application of chromanol 293B, a steady-state block of IKv developed within 135 s. The block was concentration-dependent with an IC50 of 7.4 microM. Chromanol did not produce any shift in the normalized steady-state activation and inactivation curves and the recovery from inactivation was not significantly changed. Chromanol 293B similarly inhibited delayed rectifier K+ channels whether in their closed or open state, and produced an "apparent" acceleration of inactivation, i.e., the drug accelerated the faster time constant of inactivation during a 10 s test pulse from 384 ms (control) to 149 ms (100 microM chromanol). In recent studies, chromanol was described as a specific blocker of slowly activating delayed rectifier potassium channels (IKs) in cardiomyocytes. The results of this study, however, extend the inhibitory spectrum of the drug and demonstrate block of closed and open state delayed rectifier K+ currents in portal vein vascular smooth muscle. Such a block could possibly contribute to the generation of portal hypertension.
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PMID:Vascular effects of class-III antiarrhythmic drugs: chromanol 293B, but not dofetilide blocks the smooth muscle delayed rectifier K+ channel. 1199 73

Cerebro-retinal microangiopathy with calcifications and cysts (CRMCC) or Coats plus syndrome is a pleiotropic disorder affecting the eyes, brain, bone and gastrointestinal tract. Its primary pathogenesis involves small vessel obliterative microangiopathy. Recently, autosomal recessively inherited mutations in CTC1 have been reported in CRMCC patients. We herein report an adolescent referred to our hospital following new seizures in a context of an undefined multisystem disorder. Cerebral imaging disclosed asymmetrical leukopathy, intracranial calcifications and cysts. In addition, he presented other typical CRMCC features i.e. a history of intrauterine growth retardation, skeletal demineralization and osteopenia, bilateral exudative vitreo-retinopathy reminiscent of Coats disease, recurrent gastrointestinal hemorrhages secondary to watermelon stomach and variceal bleeding of the esophagus due to idiopathic portal hypertension and telangiectatic and angiodysplasic changes in the small intestine and colon, and anemia due to recurrent bleeding and bone marrow abnormalities. The patient was diagnosed with Coats plus syndrome. CTC1 gene screening confirmed the diagnosis with the identification of heterozygous deleterious mutations. CRMCC due to CTC1 mutations has a broad clinical expressivity. Our case report illustrates the main possible associated phenotypes and their complications, demonstrating the need for a careful etiological search in order to initiate appropriate therapeutic and preventive measures.
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PMID:Cerebro-retinal microangiopathy with calcifications and cysts due to recessive mutations in the CTC1 gene. 2584 5