Potassium channels are particularly important in determining the shape and duration of the action potential, controlling the membrane potential, modulating hormone secretion, epithelial function and, in the case of those K + channels activated by Ca 2+ , damping excitatory signals. The multiplicity of roles played by K + channels is only possible to their mammoth diversity that includes at present 70 K + channels encoding genes in mammals. Today, thanks to the use of cloning, mutagenesis, and the more recent structural studies using x‐ray crystallography, we are in a unique position to understand the origins of the enormous diversity of this superfamily of ion channels, the roles they play in different cell types, and the relations that exist between structure and function. With the exception of two‐pore K + channels that are dimers, voltage‐dependent K + channels are tetrameric assemblies and share an extremely well conserved pore region, in which the ion‐selectivity filter resides. In the present overview, we discuss in the function, localization, and the relations between function and structure of the five different subfamilies of K + channels: (a) inward rectifiers, Kir; (b) four transmembrane segments‐2 pores, K 2P ; (c) voltage‐gated, Kv; (d) the Slo family; and (e) Ca 2+ ‐activated SK family, SKCa. © 2012 American Physiological Society. Compr Physiol 2:2087‐2149, 2012.

Background:The mode of action of PI(4,5)P 2 in TRPV1 is controversial. Results: Positively charged amino acids in the S4-S5 linker and in the TRP box form the PI(4,5)P 2 binding site. Conclusion: PI(4,5)P 2 is a TRPV1 agonist and induces a conformational change of the internal gate. Significance: The molecular nature of the PI(4,5)P 2 binding site in TRPV1 is defined.

Bone integrity depends on a finely tuned balance between bone synthesis by osteoblasts and resorption by osteoclasts. The secretion capacity of mature osteoblasts requires strict control of proteostasis. Endoplasmic reticulum-associated degradation (ERAD) prevents the accumulation of unfolded ER proteins via dislocation to the cytosol and degradation by the proteasome. The ER membrane protein, homocysteine-inducible endoplasmic reticulum protein with ubiquitin-like domain 1 (HERPUD1), is a key component of the ERAD multiprotein complex which helps to stabilize the complex and facilitate the efficient degradation of unfolded proteins. HERPUD1 expression is strongly up-regulated by the unfolded protein response and cellular stress. The aim of the current study was to establish whether HERPUD1 and ERAD play roles in osteoblast differentiation and maturation. We evaluated preosteoblastic MC3T3-E1 cell and primary rat osteoblast differentiation by measuring calcium deposit levels, alkaline phosphatase activity, and runt-related transcription factor 2 and osterix expression. We found that ERAD and proteasomal degradation were activated and that HERPUD1 expression was increased as osteoblast differentiation progressed. The absence of HERPUD1 blocked osteoblast mineralization in vitro and significantly reduced alkaline phosphatase activity. In contrast, HERPUD1 overexpression activated the osteoblast differentiation program. Our results demonstrate that HERPUD1 and ERAD are important for the activation of the osteoblast maturation program and may be useful new targets for elucidating bone physiology.-Américo-Da-Silva, L., Diaz, J., Bustamante, M., Mancilla, G., Oyarzún, I., Verdejo, H. E., Quiroga, C. A new role for HERPUD1 and ERAD activation in osteoblast differentiation and mineralization.