gyang Yan
Yale University
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Featured researches published by gyang Yan.
Neuropharmacology | 2006
Bo Yang; Valentin K. Gribkoff; Jennifer Qian Pan; Veronique Damagnez; Steven I. Dworetzky; Christopher G. Boissard; Arin Bhattacharjee; Yangyang Yan; Fred J. Sigworth; Leonard K. Kaczmarek
The Slack (Sequence like a calcium-activated K channel) (Slo2.2) gene is abundantly expressed in the mammalian brain and encodes a sodium-activated K+ (KNa) channel. Although the specific roles of Slack channel subunits in neurons remain to be identified, they may play a role in the adaptation of firing rate and in protection against ischemic injury. In the present study, we have generated a stable cell line expressing the Slack channel, and have analyzed the pharmacological properties of these channels in these cells and in Xenopus oocytes. Two known blockers of KNa channels, bepridil and quinidine, inhibited Slack currents in a concentration-dependent manner and decreased channel activity in excised membrane patches. The inhibition by bepridil was potent, with an IC50 of 1.0 microM for inhibition of Slack currents in HEK cells. In contrast, bithionol was found to be a robust activator of Slack currents. When applied to the extracellular face of excised patches, bithionol rapidly induced a reversible increase in channel opening, suggesting that it acts on Slack channels relatively directly. These data establish an important early characterization of agents that modulate Slack channels, a process essential for the experimental manipulation of Slack currents in neurons.
The Journal of Neuroscience | 2009
Haijun Chen; Jack Kronengold; Yangyang Yan; Valeswara-Rao Gazula; Maile R. Brown; Liqun Ma; Gonzalo Ferreira; Youshan Yang; Arin Bhattacharjee; Fred J. Sigworth; Larry Salkoff; Leonard K. Kaczmarek
Potassium channels activated by intracellular Na+ ions (KNa) play several distinct roles in regulating the firing patterns of neurons, and, at the single channel level, their properties are quite diverse. Two known genes, Slick and Slack, encode KNa channels. We have now found that Slick and Slack subunits coassemble to form heteromeric channels that differ from the homomers in their unitary conductance, kinetic behavior, subcellular localization, and response to activation of protein kinase C. Heteromer formation requires the N-terminal domain of Slack-B, one of the alternative splice variants of the Slack channel. This cytoplasmic N-terminal domain of Slack-B also facilitates the localization of heteromeric KNa channels to the plasma membrane. Immunocytochemical studies indicate that Slick and Slack-B subunits are coexpressed in many central neurons. Our findings provide a molecular explanation for some of the diversity in reported properties of neuronal KNa channels.
The Journal of Membrane Biology | 2012
Yangyang Yan; Youshan Yang; Shumin Bian; Fred J. Sigworth
The slack (slo2.2) gene codes for a potassium-channel α-subunit of the 6TM voltage-gated channel family. Expression of slack results in Na+-activated potassium channel activity in various cell types. We describe the purification and reconstitution of Slack protein and show that the Slack α-subunit alone is sufficient for potassium channel activity activated by sodium ions as assayed in planar bilayer membranes and in membrane vesicles.
The Journal of General Physiology | 2004
Youshan Yang; Yangyang Yan; Fred J. Sigworth
For structural studies it would be useful to constrain the voltage sensor of a voltage-gated channel in its deactivated state. Here we consider one Shaker potassium channel mutant and speculate about others that might allow the channel to remain deactivated at zero membrane potential. Ionic and gating currents of F370C Shaker, expressed in Xenopus oocytes, were recorded in patches with internal application of the methanethiosulfonate reagent MTSET. It appears that the voltage dependence of voltage sensor movement is strongly shifted by reaction with internal MTSET, such that the voltage sensors appear to remain deactivated even at positive potentials. A disadvantage of this construct is that the rate of modification of voltage sensors by MTSET is quite low, ∼0.17 mM−1·s−1 at −80 mV, and is expected to be much lower at depolarized potentials.
Biophysical Journal | 2010
Matthew R. Fleming; Jack Kronengold; Yangyang Yan; TuKiet T. Lam; Erol E. Gulcicek; Fred J. Sigworth; Angus C. Nairn; Leonard K. Kaczmarek
Na+-activated potassium channels (KNa channels), which are encoded by the Slack and Slick genes contribute to neuronal adaptation during sustained stimulation, and, in auditory brainstem neurons, may regulate the accuracy of timing of action potentials. These channels have been found to be modulated very potently by activation of protein kinase C (PKC) and by receptors linked to activation of this kinase. Activators of PKC increase the amplitude of Slack-B currents and slow their rate of activation, and in contrast, activation of PKC decreases the amplitude of Slick currents. Heteromeric Slack/Slick channels are regulated by PKC to a greater extent than either Slack-B or Slick heteromers (90% decrease in amplitude). Previous experiments using Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS) have identified three serine residues in Slack-B that are phosphorylated under basal conditions, but are not within consensus sites for PKC. In order to study the mechanisms of regulation of Slack and Slick channels by phosphorylation, we have begun to identify the specific residues that undergo phosphorylation by protein kinase C. Consensus sequence analysis predicts that there are 13 potential sites of possible PKC phosphorylation in the Slack-B sequence. We have constructed individual site mutants for each of these sites in which the serine/threonines have been mutated to alanines to prevent phosphorylation at these residues. These mutants were expressed in Xenopus oocytes and their response to a PKC-activating phorbol ester (TPA) was characterized by two-electrode whole cell clamp electrophysiology. Of the 13 consensus site mutants, only one generated currents that matched wild-type Slack-B currents in their amplitude and kinetic behavior, but completely failed to respond to application of TPA, suggesting that the phosphorylation state of a single residue regulates Slack-B current amplitude and rate of activation.
The Journal of General Physiology | 1997
Youshan Yang; Yangyang Yan; Fred J. Sigworth
The Journal of General Physiology | 1997
Rajesh Mathur; Jie Zheng; Yangyang Yan; Fred J. Sigworth
Biophysical Journal | 2017
Hideki Shigematsu; Youshan Yang; Yangyang Yan; Yi Chen; Fred J. Sigworth
Biophysical Journal | 2014
Hideki Shigematsu; Youshan Yang; Yangyang Yan; Katharina Duerr; Eric Gouaux; Fred J. Sigworth
Biophysical Journal | 2012
Youshan Yang; Yangyang Yan; Fred J. Sigworth