8 research outputs found
Ion channel mechanisms of rat tail artery contraction-relaxation by menthol involving, respectively, TRPM8 activation and L-type Ca2+ channel inhibition
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 nonneuronal tissues, including vasculature. We previously demonstrated that menthol causes variable mechanical responses (vasoconstriction, vasodilatation, or biphasic reactions) in isolated arteries, depending on vascular tone. Here we aimed to dissect the specific ion channel mechanisms and corresponding Ca2+ signaling pathways underlying such complex responses to menthol and other TRPM8 ligands in rat tail artery myocytes using patch-clamp electrophysiology, confocal Ca2+ imaging, and ratiometric Ca2+ recording. Menthol (300 μM, a concentration typically used to induce TRPM8 currents) strongly inhibited L-type Ca2+ channel current (L-ICa) in isolated myocytes, especially its sustained component, most relevant for depolarization-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, similar to resting (i.e., without α-adrenoceptor stimulation by PE) conditions, when L-type channels were mostly deactivated. Menthol-induced increases in PE-induced vasoconstrictions could be inhibited both by the TRPM8 antagonist AMTB (thus confirming the specific role of TRPM8) and by cyclopiazonic acid treatment to deplete Ca2+ stores, pointing to a major contribution of Ca2+ release from the sarcoplasmic reticulum in these contractile responses. Immunocytochemical analysis has indeed revealed colocalization of TRPM8 and InsP3 receptors. Moreover, menthol Ca2+ responses, which were somewhat reduced under Ca2+-free conditions, were strongly reduced by cyclopiazonic acid treatment to deplete Ca2+ store, whereas caffeine-induced Ca2+ responses were blunted in the presence of menthol. Finally, two other common TRPM8 agonists, WS-12 and icilin, also inhibited L-ICa With respect to L-ICa inhibition, WS-12 is the most selective agonist. It augmented PE-induced contractions, whereas any secondary phase of vasorelaxation (as with menthol) was completely lacking. 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. These findings will promote our understanding of the vascular TRPM8 role, especially the well-known hypotensive effect of menthol, and may also have certain translational implications (e.g., in cardiovascular surgery, organ storage, transplantation, and Raynaud's phenomenon)
Transient receptor potential melastatin member 8 calcium channel involvement in vascular contraction. - Symposium for Integrative Mammalian Biology Capacity Initiative The Universities of Glasgow and Strathclyde,
TRPM8 activation causes depolarisations accompanied by high-frequency spontaneous hyperpolarisations through a Ca2+ signalling complex with BKCa channels in rat tail artery myocytes. (Proc Physiol Soc 15 PC225). (Poster presentation)
Molecular expression and calcium signalling roles of native TRP channels in vascular cells
Molecular expression and calcium signalling roles of native TRP channels in vascular cells. Cell Membranes and Free Radical Research. The Abstract Book of 4th Int. Congress on Cell Membranes and Oxidative Stress: Focus on Calcium Signaling and TRP Channels (Oral presentation)
Molecular and functional expression of TRP melastatin member 8 channel in arterial smooth muscles. (Phys Soc Leeds “Cardiac & Respiratory Physiology Themed Meeting” 17-19 March 2008) (Oral presentation)
Molecular expression and calcium signalling roles of TRPM8 channel in arterial smooth muscles. Proceedings of the Advanced Workshop “T-type calcium channels: from discovery to channelopathies, 25 years of research”, Kiev
Nanoshaped CuO/CeO<sub>2</sub> Materials: Effect of the Exposed Ceria Surfaces on Catalytic Activity in N<sub>2</sub>O Decomposition Reaction
This study reports a thorough investigation
of nanosized CuO/CeO<sub>2</sub> materials as an efficient catalyst
for decomposition of N<sub>2</sub>O, which is a strong greenhouse
gas largely produced by chemical
industry. Effect of terminating CeO<sub>2</sub> crystalline planes
({100}, {110}, and {111}) on the behavior of CuO dispersed over CeO<sub>2</sub> nanocubes, nanorods and polyhedral crystallites was examined
in detail by using a variety of catalyst characterization techniques.
The 4 wt % Cu was found as the most advantageous metal loading, whereas
higher Cu content resulted in lower dispersion and formation of significantly
less active, segregated bulk CuO phase. It was discovered that CuO/CeO<sub>2</sub> solids should enable both excessive oxygen mobility on the
catalyst surface as well as formation of highly reducible Cu defect
sites, in order to ensure high intrinsic activity. Detailed studies
further revealed that CeO<sub>2</sub> morphology needs to be tailored
to expose {100} and {110} high-energy surface planes, as present in
CeO<sub>2</sub> nanorods. Oxygen mobility and regeneration of active
Cu phase on these surface planes is easier, which in turn facilitates
higher catalytic activity through the recombination of surface oxygen
atoms and desorption as molecular oxygen that replenishes active sites
for subsequent catalytic cycles. As a consequence, CuO supported on
CeO<sub>2</sub> nanorods demonstrated lower activation energy (87
kJ/mol) in N<sub>2</sub>O decomposition reaction compared to catalysts
based on CeO<sub>2</sub> nanocubes (102 kJ/mol) or polyhedral CeO<sub>2</sub> (92 kJ/mol)