Physiology and Pharmacology Ca V 3.1 T-Type Ca 2þ Channels Contribute to Myogenic Signaling in Rat Retinal Arterioles

PURPOSE. Although L-type Ca 2þ channels are known to play a key role in the myogenic reactivity of retinal arterial vessels, the involvement of other types of voltage-gated Ca 2þ channels in this process remains unknown. In the present study we have investigated the contribution of T-type Ca 2þ channels to myogenic signaling in arterioles of the rat retinal microcirculation. METHODS. Confocal immunolabeling of whole-mount preparations was used to investigate the localization of Ca V 3.1-3 channels in retinal arteriolar smooth muscle cells. T-type currents and the contribution of T-type channels to myogenic signaling were assessed by whole-cell patchclamp recording and pressure myography of isolated retinal arteriole segments. RESULTS. Strong immunolabeling for Ca V 3.1 was observed on the plasma membrane of retinal arteriolar smooth muscle cells. In contrast, no expression of Ca V 3.2 or Ca V 3.3 could be detected in retinal arterioles, although these channels were present on glial cell end-feet surrounding the vessels and retinal ganglion cells, respectively. TTA-A2-sensitive T-type currents were recorded in retinal arteriolar myocytes with biophysical properties distinct from those of the L-type currents present in these cells. Inhibition of T-type channels using TTA-A2 or ML-218 dilated isolated, myogenically active, retinal arterioles. CONCLUSIONS. Ca V 3.1 T-type Ca 2þ channels are functionally expressed on arteriolar smooth muscle cells of retinal arterioles and play an important role in myogenic signaling in these vessels. The work has important implications concerning our understanding of the mechanisms controlling blood flow autoregulation in the retina and its disruption during ocular disease

Characterization of Hypertension Risk Factors at the Committee on Temporary Shelter

Introduction: The health of homeless populations is at risk due to a high prevalence of undiagnosed hypertension (HTN) and cardiovascular disease (CVD). The interaction of housing and socioeconomic status with the risk factors for HTN and CVD remains unclear. Prevention of HTN through a healthy diet, exercise, adequate sleep, and avoidance of tobacco has been well described, but financial limitations and competing priorities for shelter and food make blood pressure (BP) control difficult for this population. By characterizing the risk factors and awareness of hypertension within the homeless population at the Committee on Temporary Shelter Daystation (COTS) in Burlington, Vermont, we may be able to identify promising avenues for therapeutic intervention.https://scholarworks.uvm.edu/comphp_gallery/1226/thumbnail.jp

Biodentine Reduces Tumor Necrosis Factor Alpha-induced TRPA1 Expression in Odontoblastlike Cells

International audienceIntroduction: The transient receptor potential (TRP) ion channels have emerged as important cellular sensors in both neuronal and non-neuronal cells, with TRPA1 playing a central role in nociception and neurogenic inflammation. The functionality of TRP channels has been shown to be modulated by inflammatory cytokines. The aim of this study was to investigate the effect of inflammation on odontoblast TRPA1 expression and to determine the effect of Biodentine (Septodent, Paris, France) on inflammatory-induced TRPA1 expression. Methods: Immunohistochemistry was used to study TRPA1 expression in pulp tissue from healthy and carious human teeth. Pulp cells were differentiated to odontoblastlike cells in the presence of 2 mmol/L beta-glycerophosphate, and these cells were used in quantitative polymerase chain reaction, Western blotting, calcium imaging, and patch clamp studies. Results: Immunofluorescent staining revealed. TRPA1 expression in odontoblast cell bodies and odontoblast processes, which was more intense in carious versus healthy teeth. TRPA1 gene expression was induced in cultured odontoblastlike cells by tumor necrosis factor alpha, and this expression was significantly reduced in the presence of Biodentine. The functionality of the TRPA1 channel was shown by calcium microfluorimetry and patch clamp recording, and our results showed a significant reduction in tumor necrosis factor alpha induced TRPA1 responses after Biodentine treatment. Conclusions: In conclusion, this study showed TRPA1 to be modulated by caries-induced inflammation and that Biodentine reduced TRPA1 expression and functional responses

CAMKII as a therapeutic target for growth factor-induced retinal and choroidal neovascularisation

This study was supported by grants from the British Heart Foundation (PG/11/99/29207 and PG/11/94/29169), Fight for Sight, UK (1387/88), Health & Social Care R&D Division, Northern Ireland (STL/4748/13) and the Medical Research Council (MC_PC_15026). We would like to thank Gordon Revolta for excellent assistance with colony management and genotyping.Peer reviewedPublisher PD

Incidence of WHO stage 3 and 4 conditions following initiation of Anti-Retroviral Therapy in resource limited settings

To determine the incidence of WHO clinical stage 3 and 4 conditions during early anti-retroviral therapy (ART) in resource limited settings (RLS)

Physiology and Pharmacology Feedback via Ca 2þ -Activated Ion Channels Modulates Endothelin 1 Signaling in Retinal Arteriolar Smooth Muscle

PURPOSE. To investigate the role of feedback by Ca 2þ -sensitive plasma-membrane ion channels in endothelin 1 (Et1) signaling in vitro and in vivo. METHODS. Et1 responses were imaged from Fluo-4-loaded smooth muscle in isolated segments of rat retinal arteriole using two-dimensional (2-D) confocal laser microscopy. Vasoconstrictor responses to intravitreal injections of Et1 were recorded in the absence and presence of appropriate ion channel blockers using fluorescein angiograms imaged using a confocal scanning laser ophthalmoscope. RESULTS. Et1 (10 nM) increased both basal [Ca 2þ ] i and the amplitude and frequency of Ca 2þ -waves in retinal arterioles. The Ca 2þ -activated Cl --channel blockers DIDS and 9-anthracene carboxylic acid (9AC) blocked Et1-induced increases in wave frequency, and 9AC also inhibited the increase in amplitude. Iberiotoxin, an inhibitor of large conductance (BK) Ca 2þ -activated K þ -channels, increased wave amplitude in the presence of Et1 but had no effect on frequency