Biology subjects

Chuang, H.-h.

Publications and source records attributed to Chuang, H.-h..

2 recordsLinked to original sources

bioRxiv2020

G protein-Coupled Receptor Distribution Impacts the Effectiveness of Signal Transmission.

Numbers of activated receptor dictate efficacy of neurotransmitter stimulation. Many PLC coupled receptors activated by ligands elicit canonical downstream Gq/11 pathway to induce endogenous Ca2+ gated chloride channels. The coupling from receptors to effectors was analyzed in Xenopus oocytes expressing genetically modified angiotensin receptor type 1 receptor (AT1R). The latency between ATII binding and Ca2+-induced Cl- current surge was inversely correlated. AT1R activation triggered a chain of chemical reactions, of which the products were playing messengers for subsequent events. Messenger accumulation must rate-limit the agonism. For accurate quantification the speed of ATII triggered the i Cl-. The T-form AT1R-IRK1 fusion exhibits faster induction compared to the M-form. The latency of the recorded none vanished i Cl-, marking the lowest genuine calcium activation, took place at earlier time point by the timer time. The evoked i Cl- however reached similar maximal amplitudes. This kinetic effect raises the possibility to use temporal coding to complement amplitude coding (analogous to FM versus AM radio transmission) for receptor-agonist pairs.

neuroscience↗

bioRxiv2019

It takes two vanilloid ligand bindings per channel to transduce painful capsaicin stimuli

The capsaicin receptor TRPV1 in mammals evolved the capability of integrating pain arising from combinations of noxious temperature or chemical irritants. Four-fold repetition of TRPV1 subunits makes an ion channel endowed with excellent sensitivity for pain detection, assisting this ionotropic receptor to differentiate graded injuries. We manipulated the stoichiometry and relative steric coordination of capsaicin binding at the molecular level, explicating rules with which a receptor codes pain within a broad range of intensity. The first ligand binding delivers small but clear initiation of channel activation. Maximal agonist action has already been reached in a receptor-in-tandem containing two or three wild-type receptor units, displaying activity comparable to the full liganded all-wild-type tandem tetramers. When the binding sites outnumbered ligands, independent action dominates in each channel. The non-vanilloid agonist 2-APB differs from capsaicin by adopting a distinct open mechanism since it does not demand a vanilloid group to activate. The sharing of the same pore greatly simplifies synergism to transduce relevant inputs by summation for pain signaling. And questions the need to explore deeper into other aspects of nociception.

molecular biology↗