Ion channels as effectors in carbon monoxide signaling

A wealth of recent studies has highlighted the diverse and important influences of carbon monoxide (CO) on cellular signaling pathways. Such studies have implicated CO, and the enzymes from which it is derived (heme oxygenases) as potential therapeutic targets, particularly (although not exclusively) in inflammation, immunity and cardiovascular disease.1 In a recent study,2 we demonstrated that CO inhibited cardiac L-type Ca(2+) channels. This effect arose due to the ability of CO to bind to mitochondria (presumably at complex IV of the electron transport chain) and so cause electron leak, which resulted in increased production of reactive oxygen species. These modulated the channel's activity through interactions with three cysteine residues in the cytosolic C-terminus of the channel's major, pore-forming subunit. Our study provided a potential mechanism for the cardioprotective effects of CO and also highlighted ion channels as a major potential target group for this gasotransmitter.

Diverse mechanisms underlying the regulation of ion channels by carbon monoxide

Carbon monoxide is firmly established as an important, physiological signalling molecule as well as a potent toxin. Through its ability to bind metal-containing proteins it is known to interfere with a number of intracellular signalling pathways, and such actions can account for its physiological and pathological effects. In particular, CO can modulate the intracellular production of reactive oxygen species, nitric oxide and cGMP levels, as well as regulate MAP kinase signalling. In this review, we consider ion channels as more recently discovered effectors of CO signalling. CO is now known to regulate a growing number of different ion channel types, and detailed studies of the underlying mechanisms of action are revealing unexpected findings. For example, there are clear areas of contention surrounding its ability to increase the activity of high conductance, Ca2+ -sensitive K+ channels. More recent studies have revealed the ability of CO to inhibit T-type Ca2+ channels and have unveiled a novel signalling pathway underlying tonic regulation of this channel. It is clear that the investigation of ion channels as effectors of CO signalling is in its infancy, and much more work is required to fully understand both the physiological and the toxic actions of this gas. Only then can its emerging use as a therapeutic tool be fully and safely exploited.

Diverse mechanisms underlying the regulation of ion channels by carbon monoxide

Carbon monoxide (CO) is firmly established as an important, physiological signalling molecule as well as a potent toxin. Through its ability to bind metal-containing proteins, it is known to interfere with a number of intracellular signalling pathways, and such actions can account for its physiological and pathological effects. In particular, CO can modulate the intracellular production of reactive oxygen species, NO and cGMP levels, as well as regulate MAPK signalling. In this review, we consider ion channels as more recently discovered effectors of CO signalling. CO is now known to regulate a growing number of different ion channel types, and detailed studies of the underlying mechanisms of action are revealing unexpected findings. For example, there are clear areas of contention surrounding its ability to increase the activity of high conductance, Ca2+ -sensitive K+ channels. More recent studies have revealed the ability of CO to inhibit T-type Ca2+ channels and have unveiled a novel signalling pathway underlying tonic regulation of this channel. It is clear that the investigation of ion channels as effectors of CO signalling is in its infancy, and much more work is required to fully understand both the physiological and the toxic actions of this gas. Only then can its emerging use as a therapeutic tool be fully and safely exploited.

Complete filling of zeolite frameworks with polyalkynes formed in situ by transition-metal ion catalysts

We report the use of transition-metal-exchanged zeolites as media for the catalytic formation and encapsulation of both polyethyne and polypropyne, and computer modeling studies on the composites so formed. Alkyne gas was absorbed into the pores of zeolite Y (Faujasite) exchanged with transition-metal cations [Fe(II), Co(II), Cu(II), Ni(II), and Zn(II)]. Ni(II) and Zn(II) were found to be the most efficient for the production of poly-ynes. These cations were also found to be effective in polymer generation when exchanged in zeolites mordenite and beta. The resulting powdered samples were characterized by FTIR, Raman, diffuse reflectance electronic spectroscopy, TEM, and elemental analysis, revealing, nearly complete loading of the zeolite channels for the majority of the samples. Based on the experimental carbon content, we have derived the percentage of channel filling, and the proportion of the channels containing a single polymer chain for mordenite. Experimentally, the channels for Y are close to complete filling for polyethyne (PE) and polypropyne (PP), and this is also true for polyethyne in mordenite. Computer modeling studies using Cerius2 show that the channels of mordenite can only accept a single polymer chain of PP, in which case these channels are also completely filled.

Acidity controls on dissolved organic carbon mobility in organic soils

Dissolved organic carbon (DOC) concentrations in surface waters have increased across much of Europe and North America, with implications for the terrestrial carbon balance, aquatic ecosystem functioning, water treatment costs and human health. Over the past decade, many hypotheses have been put forward to explain this phenomenon, from changing climate and land-management to eutrophication and acid deposition. Resolution of this debate has been hindered by a reliance on correlative analyses of time-series data, and a lack of robust experimental testing of proposed mechanisms. In a four-year, four-site replicated field experiment involving both acidifying and de-acidifying treatments, we tested the hypothesis that DOC leaching was previously suppressed by high levels of soil acidity in peat and organo-mineral soils, and therefore that observed DOC increases a consequence of decreasing soil acidity. We observed a consistent, positive relationship between DOC and acidity change at all sites. Responses were described by similar hyperbolic relationships between standardised changes in DOC and hydrogen ion concentrations at all sites, suggesting potentially general applicability. These relationships explained a substantial proportion of observed changes in peak DOC concentrations in nearby monitoring streams, and application to a UK-wide upland soil pH dataset suggests that recovery from acidification alone could have led to soil solution DOC increases in the range 46-126% by habitat type since 1978. Our findings raise the possibility that changing soil acidity may have wider impacts on ecosystem carbon balances. Decreasing sulphur deposition may be accelerating terrestrial carbon loss, and returning surface waters to a natural, high-DOC condition.