Sensory neuron sodium channel Nav1.8 is essential for pain at low temperatures

Sensory acuity and motor dexterity deteriorate when human limbs cool down, but pain perception persists and cold-induced pain can become excruciating. Evolutionary pressure to enforce protective behaviour requires that damage-sensing neurons (nociceptors) continue to function at low temperatures. Here we show that this goal is achieved by endowing superficial endings of slowly conducting nociceptive fibres with the tetrodotoxin-resistant voltage-gated sodium channel (VGSC) Na(v)1.8 (ref. 2). This channel is essential for sustained excitability of nociceptors when the skin is cooled. We show that cooling excitable membranes progressively enhances the voltage-dependent slow inactivation of tetrodotoxin-sensitive VGSCs. In contrast, the inactivation properties of Na(v)1.8 are entirely cold-resistant. Moreover, low temperatures decrease the activation threshold of the sodium currents and increase the membrane resistance, augmenting the voltage change caused by any membrane current. Thus, in the cold, Na(v)1.8 remains available as the sole electrical impulse generator in nociceptors that transmits nociceptive information to the central nervous system. Consistent with this concept is the observation that Na(v)1.8-null mutant mice show negligible responses to noxious cold and mechanical stimulation at low temperatures. Our data present strong evidence for a specialized role of Na(v)1.8 in nociceptors as the critical molecule for the perception of cold pain and pain in the cold.     

Stream denitrification across biomes and its response to anthropogenic nitrate loading

Anthropogenic addition of bioavailable nitrogen to the biosphere is increasing and terrestrial ecosystems are becoming increasingly nitrogen-saturated, causing more bioavailable nitrogen to enter groundwater and surface waters. Large-scale nitrogen budgets show that an average of about 20-25 per cent of the nitrogen added to the biosphere is exported from rivers to the ocean or inland basins, indicating that substantial sinks for nitrogen must exist in the landscape. Streams and rivers may themselves be important sinks for bioavailable nitrogen owing to their hydrological connections with terrestrial systems, high rates of biological activity, and streambed sediment environments that favour microbial denitrification. Here we present data from nitrogen stable isotope tracer experiments across 72 streams and 8 regions representing several biomes. We show that total biotic uptake and denitrification of nitrate increase with stream nitrate concentration, but that the efficiency of biotic uptake and denitrification declines as concentration increases, reducing the proportion of in-stream nitrate that is removed from transport. Our data suggest that the total uptake of nitrate is related to ecosystem photosynthesis and that denitrification is related to ecosystem respiration. In addition, we use a stream network model to demonstrate that excess nitrate in streams elicits a disproportionate increase in the fraction of nitrate that is exported to receiving waters and reduces the relative role of small versus large streams as nitrate sinks.