57 research outputs found

    HL-1 cells express an inwardly rectifying K+ current activated via muscarinic receptors comparable to that in mouse atrial myocytes

    Get PDF
    An inwardly rectifying K^+ current is present in atrial cardiac myocytes that is activated by acetylcholine (I_{KACh}). Physiologically, activation of the current in the SA node is important in slowing the heart rate with increased parasympathetic tone. It is a paradigm for the direct regulation of signaling effectors by the Gβγ G-protein subunit. Many questions have been addressed in heterologous expression systems with less focus on the behaviour in native myocytes partly because of the technical difficulties in undertaking comparable studies in native cells. In this study, we characterise a potassium current in the atrial-derived cell line HL-1. Using an electrophysiological approach, we compare the characteristics of the potassium current with those in native atrial cells and in a HEK cell line expressing the cloned Kir3.1/3.4 channel. The potassium current recorded in HL-1 is inwardly rectifying and activated by the muscarinic agonist carbachol. Carbachol-activated currents were inhibited by pertussis toxin and tertiapin-Q. The basal current was time-dependently increased when GTP was substituted in the patch-clamp pipette by the non-hydrolysable analogue GTPγS. We compared the kinetics of current modulation in HL-1 with those of freshly isolated atrial mouse cardiomyocytes. The current activation and deactivation kinetics in HL-1 cells are comparable to those measured in atrial cardiomyocytes. Using immunofluorescence, we found GIRK4 at the membrane in HL-1 cells. Real-time RT-PCR confirms the presence of mRNA for the main G-protein subunits, as well as for M2 muscarinic and A1 adenosine receptors. The data suggest HL-1 cells are a good model to study IKAch

    Urine steroid metabolomics for the differential diagnosis of adrenal incidentalomas in the EURINE-ACT study: a prospective test validation study

    Get PDF

    Pituitary-hormone secretion by thyrotropinomas

    Get PDF
    Hormone secretion by somatotropinomas, corticotropinomas and prolactinomas exhibits increased pulse frequency, basal and pulsatile secretion, accompanied by greater disorderliness. Increased concentrations of growth hormone (GH) or prolactin (PRL) are observed in about 30% of thyrotropinomas leading to acromegaly or disturbed sexual functions beyond thyrotropin (TSH)-induced hyperthyroidism. Regulation of non-TSH pituitary hormones in this context is not well understood. We there therefore evaluated TSH, GH and PRL secretion in 6 patients with up-to-date analytical and mathematical tools by 24-h blood sampling at 10-min intervals in a clinical research laboratory. The profiles were analyzed with a new deconvolution method, approximate entropy, cross-approximate entropy, cross-correlation and cosinor regression. TSH burst frequency and basal and pulsatile secretion were increased in patients compared with controls. TSH secretion patterns in patients were more irregular, but the diurnal rhythm was preserved at a higher mean with a 2.5 h phase delay. Although only one patient had clinical acromegaly, GH secretion and IGF-I levels were increased in two other patients and all three had a significant cross-correlation between the GH and TSH. PRL secretion was increased in one patient, but all patients had a significant cross-correlation with TSH and showed decreased PRL regularity. Cross-ApEn synchrony between TSH and GH did not differ between patients and controls, but TSH and PRL synchrony was reduced in patients. We conclude that TSH secretion by thyrotropinomas shares many characteristics of other pituitary hormone-secreting adenomas. In addition, abnormalities in GH and PRL secretion exist ranging from decreased (joint) regularity to overt hypersecretion, although not always clinically obvious, suggesting tumoral transformation of thyrotrope lineage cells

    Hemodynamic Changes in Patients with Arteriovenous Malformations Assessed Using High-Resolution 3D Radial Phase-Contrast MR Angiography

    Get PDF
    BACKGROUND AND PURPOSE: Arteriovenous malformations have a high lifetime risk of hemorrhage; however, treatment carries a significant risk of morbidity and mortality, including permanent neurologic sequelae. WSS and other hemodynamic parameters are altered in patients with symptomatic AVMs, and analysis of hemodynamics may have value in stratifying patients into different risk groups. In this study, we examined hemodynamic data from patients with stable symptoms and those who pre-sented with acute symptoms to identify trends which may help in risk stratification. MATERIALS AND METHODS: Phase-contrast MRA using a radial readout (PC-VIPR) is a fast, high-resolution technique that can acquire whole-brain velocity-encoded angiograms with scan times of approximately 5 minutes. Ten patients with AVMs were scanned using PC-VIPR; velocity, area, flow, and WSS in vessels feeding the AVMs and normal contralateral vessels were calculated using velocity data from the phase-contrast acquisition. RESULTS: Patients with an asymptomatic presentation or mild symptoms (n 4) had no significant difference in WSS in feeding vessels compared with normal contralateral vessels, whereas patients presenting with hemorrhage, severe headaches/seizures, or focal neurologic deficits (n 6) had significantly higher WSS in feeding vessels compared with contralateral vessels
    corecore