Kuo Chung-Chin 郭鐘金 – NTU Neuroscience

郭鐘金

Chung-Chin Kuo

Lab Introduction & Major Research Interests

Our primary research interests are molecular physiology/pharmacology of ion channels, and the application of electrophysiological rationales to the understanding of behaviors. The experimental approaches chiefly involves electrophysiological recordings from single channels, outside-out or inside-out patches, single oocytes or dissociated neurons, brain slices, and intact brains (i.e. in vivo recordings) based on sharp-electrode or patch- clamp techniques. We have endeavored to study animal behaviors, with concomitant electrophysiological recordings or interventions at different brain areas. Recently we have made progress in the understanding of the biophysical attributes (including gating and ion permeation) of both voltage- and ligand-gated channels such as Shaker K+ channels, Na+ channels, and glutamate receptor (e.g. NMDA) channels. We have also established the causal relation between subthalamic burst discharges and parkinsonian locomotor deficits, and found that T-type Ca2+ channel blockers may readily abolish subthalamic burst discharges and remedy parkinsonian symptoms. Accordingly, hyperpolarization of the subthalamic nucleus alleviates hyperkinetic movement disorders injection of hyperpolarizing currents. The molecular and network bases of epilepto- and icto-genesis are also currently under investigation.

Recent Representative Publication ( * corresponding author)

1. Yang, Y.-C., Lin, S., Chang, P.-C., Lin, H.-C., and Kuo, C.-C. (2011) Functional extension of amino acid triads from the fourth transmembrane segment (S4) into its external linker in Shaker K+ channels. Journal of Biological Chemistry 286:37503-37514

2. Tai, C.-H., Pan, M.-K., Lin, J.-J., Huang, C.-S., Yang, Y.-C., and Kuo, C.-C. (2012) Subthalamic discharges as a causal determinant of parkinsonian motor deficits. Annals of Neurology 72:464-476

3. Pan, M.-K., Tai, C.-H., Lin, W.-C., Pei, J.-C., Lai, W.-S., and Kuo, C.-C. (2014) Deranged NMDAergic cortico-subthalamic transmission underlies parkinsonian motor deficits. Journal of Clinical Investigation 124(10):4629-4641

4. Huang, C.-W., and Kuo, C.-C. (2015) Flow- and voltage-dependent blocking effect of ethosuximide on the inward rectifier K+ (Kir2.1) channel. Pflugers Arch – Eur J Physiology 467(8):1733-1746

5. Tu, Y.-C., and Kuo, C.-C. (2015) The differential contribution of GluN1 and GluN2 to the gating operation of the NMDA receptor channel. Pflugers Arch – Eur J Physiology 467(9):1899-1917

6. Huang, C.-W., Lai, H.-J., Huang, P.-Y., Lee, M.-J., and Kuo, C.-C. (2016) The biophysical basis underlying gating changes in the p.V1316A mutant Nav1.7 channel and the molecular pathogenesis of inherited erythromelalgia. PLoS Biology 14(9): e1002561.

7. Pan, M.-K., Kuo, S.-H., Tai, C.-H., Liou, J.-Y., Pei, J.-C., Chang, C.-Y., Wang, Y.-M., Liu, W.-C., Wang, T.-R., Lai, W.-S., and Kuo, C.-C. (2016) Neuronal firing patterns outweigh circuitry oscillations in parkinsonian motor control. Journal of Clinical Investigation 126(12):4516-4526

8. Lo, Y.-T., and Kuo, C.-C. (2019) Temperature dependence of the biophysical mechanisms underlying the inhibition and enhancement effect of amiodarone on hERG channels. Molecular Pharmacology 96:330-344

9. Y-S Chen, Y-C Tu, Y-C Lai, Erin Liu, Y-C Yang, and Kuo, C.-C. (2019) Desensitization of NMDA channels requires ligand binding to both GluN1 and GluN2 subunits to constrict the pore beside the activation gate. Journal of Neurochemistry 153:549–566.

10. C-H Tai, M-K Pan, S-H Tseng, T-R Wang, and Kuo, C.-C. (2020) Hyperpolarization of the subthalamic nucleus alleviates hyperkinetic movement disorders. Scientific Reports 10:8278

11. Y-S Peng, H-T Wu, Y-C Lai, J-L Chen, Y-C Yang, and C-C Kuo (2020) Inhibition of neuronal Na+ currents by lacosamide: differential binding affinity and kinetics to different inactivated states. Neuropharmacology, in press