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The placenta is required to transport calcium (Ca.sup.2+) from mother to fetus during fetal bone mineralization. In an attempt to clarify the molecular basis of Ca.sup.2+ entry for this transport, we identified TRPM6 as a candidate for apical Ca.sup.2+ entry pathway. TRPM6 mRNA increased during the last 4 days of pregnancy, coinciding with fetal bone mineralization in mice. TRPM6 mRNA and protein was localized in the trophoblasts in labyrinth where the maternal-fetal Ca.sup.2+ transport occurs. In patch-clamp recordings, we observed TRPM6/TRPM7-like currents in mouse trophoblasts after starting fetal bone mineralization but not before mineralization. Plasma membrane Ca.sup.2+ permeability was significantly increased in TRPM6/TRPM7 expressed HEK293 cells under physiological Mg.sup.2+ and ATP concentration but not in TRPM6 or TRPM7 homomer-expressing cells. These results suggest that TRPM6 is functionally expressed in mouse placental trophoblasts, implicating in maternal-fetal Ca.sup.2+ transport likely with TRPM7, which might enable to sustain fetal bone mineralization. Keywords: TRPM6, TRPM7, Maternal-fetal calcium transport, Placenta, Trophoblasts, Author(s): Yoshiro Suzuki[sup.1,2], Masaki Watanabe[sup.1,3], Claire T. Saito[sup.1] and Makoto Tominaga[sup.1,2] Introduction Calcium (Ca[sup.2+]) has essential roles in fetal growth and development. Fetal blood Ca[sup.2+] concentration is maintained for the [...]

Ambient temperature fluctuations are detected via the thermosensory system which allows animals to seek preferable thermal conditions or escape from harmful temperatures. Evolutionary changes in thermal perception have thus potentially played crucial roles in niche selection. The genus Xenopus (clawed frog) is suitable for investigating the relationship between thermal perception and niche selection due to their diverse latitudinal and altitudinal distributions. Here we performed comparative analyses of the neuronal heat sensors TRPV1 and TRPA1 among closely related Xenopus species (X. borealis, X. muelleri, X. laevis, and X. tropicalis) to elucidate their functional evolution and to assess whether their functional differences correlate with thermal niche selection among the species. Comparison of TRPV1 among four extant Xenopus species and reconstruction of the ancestral TRPV1 revealed that TRPV1 responses to repeated heat stimulation were specifically altered in the lineage leading to X. tropicalis which inhabits warmer niches. Moreover, the thermal sensitivity of TRPA1 was lower in X. tropicalis than the other species, although the thermal sensitivity of TRPV1 and TRPA1 was not always lower in species that inhabit warmer niches than the species inhabit cooler niches. However, a clear correlation was found in species differences in TRPA1 activity. Heat‐evoked activity of TRPA1 in X. borealis and X. laevis, which are adapted to cooler niches, was significantly higher than in X. tropicalis and X. muelleri which are adapted to warmer niches. These findings suggest that the functional properties of heat sensors changed during Xenopus evolution, potentially altering the preferred temperature ranges among species. [ABSTRACT FROM AUTHOR]

Temperature is one of the most critical environmental factors affecting survival, and thus species that inhabit different thermal niches have evolved thermal sensitivities suitable for their respective habitats. During the process of shifting thermal niches, various types of genes expressed in diverse tissues, including those of the peripheral to central nervous systems, are potentially involved in the evolutionary changes in thermosensation. To elucidate the molecular mechanisms behind the evolution of thermosensation, thermal responses were compared between two species of clawed frogs (Xenopus laevis and Xenopus tropicalis) adapted to different thermal environments. X. laevis was much more sensitive to heat stimulation than X. tropicalis at the behavioral and neural levels. The activity and sensitivity of the heat-sensing TRPA1 channel were higher in X. laevis compared with those of X. tropicalis. The thermal responses of another heat-sensing channel, TRPV1, also differed between the two Xenopus species. The species differences in Xenopus TRPV1 heat responses were largely determined by three amino acid substitutions located in the first three ankyrin repeat domains, known to be involved in the regulation of rat TRPV1 activity. In addition, Xenopus TRPV1 exhibited drastic species differences in sensitivity to capsaicin, contained in chili peppers, between the two Xenopus species. Another single amino acid substitution within Xenopus TRPV1 is responsible for this species difference, which likely alters the neural and behavioral responses to capsaicin. These combined subtle amino acid substitutions in peripheral thermal sensors potentially serve as a driving force for the evolution of thermal and chemical sensation. [ABSTRACT FROM AUTHOR]