Effects of menthol on rat tail artery mediated by TRPM8 and voltage-gated calcium channels

Transient receptor potential melastatin 8 (TRPM8) is the principal cold and menthol receptor channel. Characterized primarily for its cold sensing role in sensory neurons, it is expressed and functional in several non-neuronal tissues, including vasculature. We previously demonstrated that menthol causes vasoconstriction and vasodilatation in isolated arteries, depending on vascular tone. Here we investigated calcium's role in responses mediated by TRPM8 ligands in rat tail artery myocytes using patch-clamp electrophysiology and ratiometric Ca2+ recording. Isometric contraction studies examined actions of TRPM8 ligands in the presence/absence of L-type calcium channel blocker. Menthol (300 μM), a concentration typically used to induce TRPM8 currents, strongly inhibited L-type voltage-dependent Ca2+ current (L-ICa) in myocytes, especially it's sustained component, most relevant for depolarisation-induced vasoconstriction. In contraction studies, with nifedipine present (10 μM) to abolish L-ICa contribution to phenylephrine (PE)-induced vasoconstrictions of vascular rings, a marked increase in tone was observed with menthol. Menthol-induced increases in PE-induced vasoconstrictions were mediated predominantly by Ca2+-release from sarcoplasmic reticulum, since they were significantly inhibited by cyclopiazonic acid. Pre-incubation of vascular rings with a TRPM8 antagonist strongly inhibited menthol-induced increases in PE-induced vasoconstrictions, thus confirming specific role of TRPM8. Finally, two other common TRPM8 agonists, WS-12 and icilin, inhibited L-ICa. Thus, TRPM8 channels are functionally active in rat tail artery myocytes and play a distinct direct stimulatory role in control of vascular tone. However, indirect effects of TRPM8 agonists, which are unrelated to TRPM8, are mediated by inhibition of L-type Ca2+ channels, and largely obscure TRPM8-mediated vasoconstriction.

Constant wall heat flux boundary conditions in micro-channels filled with porous material with internal heat generation under local thermal non-equilibrium conditions

Forced convection heat transfer in a micro-channel filled with a porous material saturated with rarefied gas with internal heat generation is studied analytically in this work. The study is performed by analysing the boundary conditions for constant wall heat flux under local thermal non-equilibrium (LTNE) conditions. Invoking the velocity slip and temperature jump, the thermal behaviour of the porous-fluid system is studied by considering thermally and hydrodynamically fully-developed conditions. The flow inside the porous material is modelled by the Darcy–Brinkman equation. Exact solutions are obtained for both the fluid and solid temperature distributions for two primary approaches models A and B using constant wall heat flux boundary conditions. The temperature distributions and Nusselt numbers for models A and B are compared, and the limiting cases resulting in the convergence or divergence of the two models are also discussed. The effects of pertinent parameters such as fluid to solid effective thermal conductivity ratio, Biot number, Darcy number, velocity slip and temperature jump coefficients, and fluid and solid internal heat generations are also discussed. The results indicate that the Nusselt number decreases with the increase of thermal conductivity ratio for both models. This contrasts results from previous studies which for model A reported that the Nusselt number increases with the increase of thermal conductivity ratio. The Biot number and thermal conductivity ratio are found to have substantial effects on the role of temperature jump coefficient in controlling the Nusselt number for models A and B. The Nusselt numbers calculated using model A change drastically with the variation of solid internal heat generation. In contrast, the Nusselt numbers obtained for model B show a weak dependency on the variation of internal heat generation. The velocity slip coefficient has no noticeable effect on the Nusselt numbers for both models. The difference between the Nusselt numbers calculated using the two models decreases with an increase of the temperature jump coefficient.

TRPV2 Channels Contribute to Stretch-Activated Cation Currents and Myogenic Constriction in Retinal Arterioles

Purpose: Activation of the transient receptor potential channels, TRPC6, TRPM4, and TRPP1 (PKD2), has been shown to contribute to the myogenic constriction of cerebral arteries. In the present study we sought to determine the potential role of various mechanosensitive TRP channels to myogenic signaling in arterioles of the rat retina.

Methods: Rat retinal arterioles were isolated for RT-PCR, Fura-2 Ca2+ microfluorimetry, patch-clamp electrophysiology, and pressure myography studies. In some experiments, confocal immunolabeling of wholemount preparations was used to examine the localization of specific mechanosensitive TRP channels in retinal vascular smooth muscle cells (VSMCs).

Results: Reverse transcription-polymerase chain reaction analysis demonstrated mRNA expression for TRPC1, M7, V1, V2, V4, and P1, but not TRPC6 or M4, in isolated retinal arterioles. Immunolabeling revealed plasma membrane, cytosolic and nuclear expression of TRPC1, M7, V1, V2, V4, and P1 in retinal VSMCs. Hypoosmotic stretch-induced Ca2+ influx in retinal VSMCs was reversed by the TRPV2 inhibitor tranilast and the nonselective TRPP1/V2 antagonist amiloride. Inhibitors of TRPC1, M7, V1, and V4 had no effect. Hypoosmotic stretch-activated cation currents were similar in Na+ and Cs+ containing solutions suggesting no contribution by TRPP1 channels. Direct plasma membrane stretch triggered cation current activity that was blocked by tranilast and specific TRPV2 pore-blocking antibodies and mimicked by the TRPV2 activator, Δ9-tetrahydrocannabinol. Preincubation of retinal arterioles with TRPV2 blocking antibodies prevented the development of myogenic tone.

Conclusions: Our results suggest that retinal VSMCs express a range of mechanosensitive TRP channels, but only TRPV2 appears to contribute to myogenic signaling in this vascular bed.

The art of building trust via e-communication channels: Post-acquisition integration as a special context

This study discusses the importance of establishing trust in post-acquisition integration context and how the use of e-channels facilitates or inhibits this process. The objective of this study is to analyze how the use of electronic communication channels influences the post-acquisition integration process in terms of trust establishment and overall integration efficiency, developing a framework as a result. Three sub-objectives are introduced: to find out the building blocks of trust in M&A’s, to analyse how the use of e-channels influence the process of trust establishment in post-acquisition integration context, and to define the consequences trust and use of e-channels have for the process. The theoretical background of the study includes literature and theories relating to trust establishment in post-acquisition integration context and how the use of e-channels influences the process of trust development on a general level. The empirical research is conducted as a single case study, based on key informant interviews. The interview data was collected between October 2015 and January 2016. Altogether nine interviews were realised; six with representatives from the acquiring firm and three with target firm members. Thematic analysis was selected as the main method for analysing and processing the qualitative data. This study finds that trust has an essential role in post-acquisition integration context, facilitating the integration process in various different ways. Hence, identifying the different building blocks of trust is important in order for members of the organisations to be better able establish and maintain trust. In today’s international business, the role of electronic communication channels has also increased in importance significantly and it was confirmed that these pose both challenges and possibilities for the development of interpersonal trust. One of the most important underlying factors influencing the trust levels via e-communication channels is the level of user’s comfort in using the different e-channels. Without sufficient and meaningful training, the communication conducted via these channels in inhibited in a number of ways. Hence, understanding the defining characteristics of e-communication together with the risks and opportunities related to the use of these can have far-reaching consequences for the post-acquisition integration process as a whole. The framework based on the findings and existing theory introduces the most central factors influencing the trust establishment together with the positive and negative consequences these have for the integration process. Moreover, organizational level consistency and the existence of shared guidelines on appropriate selection of communication channels according to the nature of the task at hand are seen as important

Random Access over Multi-Packet Reception Channels: A Mean-Field Approach

Thesis (Ph.D.)--University of Washington, 2016-06

Radio-Frequency Interference Identification Over Oceans for C- and X-Band AMSR2 Channels

A new method for radio-frequency interference (RFI) contamination identification over open oceans for the two C-subbands and X-band of Advanced Microwave Scanning Radiometer 2 (AMSR2) channel measurements is suggested. The method is based both on the AMSR2 brightness temperature (T-B) modeling and on the analysis of AMSR2 measurements over oceans. The joint analysis of T-B spectral differences allowed to identify the relations between them and the limits of their variability, which are ensured by the changes in the environmental conditions. It was found that the constraints, based on the ratio of spectral differences, are more regionally and seasonally independent than the spectral differences themselves. Although not all possible RFI combinations are considered, the developed simple criteria can be used to detect most RFI-contaminated pixels over the World Ocean for AMSR2 measurements in two C-subbands and the X-band.