Understand spiciness: mechanism of TRPV1 channel activation by capsaicin.

Capsaicin in chili peppers bestows the sensation of spiciness. Since the discovery of its receptor, transient receptor potential vanilloid 1 (TRPV1) ion channel, how capsaicin activates this channel has been under extensive investigation using a variety of experimental techniques including mutagenesis, patch-clamp recording, crystallography, cryo-electron microscopy, computational docking and molecular dynamic simulation. A framework of how capsaicin binds and activates TRPV1 has started to merge: capsaicin binds to a pocket formed by the channel's transmembrane segments, where it takes a "tail-up, head-down" configuration. Binding is mediated by both hydrogen bonds and van der Waals interactions. Upon binding, capsaicin stabilizes the open state of TRPV1 by "pull-and-contact" with the S4-S5 linker. Understanding the ligand-host interaction will greatly facilitate pharmaceutical efforts to develop novel analgesics targeting TRPV1

High temperature sensitivity is intrinsic to voltage-gated potassium channels.

Temperature-sensitive transient receptor potential (TRP) ion channels are members of the large tetrameric cation channels superfamily but are considered to be uniquely sensitive to heat, which has been presumed to be due to the existence of an unidentified temperature-sensing domain. Here we report that the homologous voltage-gated potassium (Kv) channels also exhibit high temperature sensitivity comparable to that of TRPV1, which is detectable under specific conditions when the voltage sensor is functionally decoupled from the activation gate through either intrinsic mechanisms or mutations. Interestingly, mutations could tune Shaker channel to be either heat-activated or heat-deactivated. Therefore, high temperature sensitivity is intrinsic to both TRP and Kv channels. Our findings suggest important physiological roles of heat-induced variation in Kv channel activities. Mechanistically our findings indicate that temperature-sensing TRP channels may not contain a specialized heat-sensor domain; instead, non-obligatory allosteric gating permits the intrinsic heat sensitivity to drive channel activation, allowing temperature-sensitive TRP channels to function as polymodal nociceptors

Error Performance of Channel Coding in Random Access Communication

A new channel coding approach was proposed in [1] for random multiple access communication over the discrete-time memoryless channel. The coding approach allows users to choose their communication rates independently without sharing the rate information among each other or with the receiver. The receiver will either decode the message or report a collision depending on whether reliable message recovery is possible. It was shown that, asymptotically as the codeword length goes to infinity, the set of communication rates supporting reliable message recovery can be characterized by an achievable region which equals Shannon's information rate region possibly without a convex hull operation. In this paper, we derive achievable bounds on error probabilities, including the decoding error probability and the collision miss detection probability, of random multiple access systems with a finite codeword length. Achievable error exponents are obtained by taking the codeword length to infinity.Comment: submitted to IEEE Transactions on Information Theor