Yu-Fung Lin, Ph.D.
4144 Tupper Hall
Our long-term research goal is to understand at a molecular level how ion channels are modulated by novel mechanisms and how we may manipulate channel regulation to treat diseases and protect cells from ischemic insults. In particular, we are interested in the ATP-sensitive potassium (KATP) channel, a high-fidelity metabolic sensor which sets membrane excitability to match cellular energy demand. Defects of KATP channel functionality are associated with diseases or pathophysiological states such as hypertension, vasospasm, diabetes mellitus, congenital hyperinsulinism, seizure, dilated cardiomyopathy, and ischemic/reperfusion injury. Our current work focuses on delineating the molecular mechanism and intracellular signaling pathway responsible for functional regulation of KATP channels by cyclic-nucleotide-dependent kinases and calcium. Other lines of research in my laboratory include studies of the role of KATP channels in ischemic preconditioning and regulation of GABA(A) receptors by novel messengers.
Zhang, D.M, Chai, Y., Erickson, J., Brown, J.H., Bers, D.M. and Lin, Y.F. Intracellular signaling mechanism responsible for modulation of sarcolemmal ATP-sensitive potassium channels by nitric oxide in ventricular cardiomyocytes. J. Physiol. (London) 2014 Mar 1;592: 971-990.
Chai, Y., Zhang, D.M. and Lin, Y.F. Activation of cGMP-dependent protein kinase stimulates cardiac ATP-sensitive potassium channels via a ROS/calmodulin/CaMKII signaling cascade. PLoS ONE 2011 Mar 29;6(3): e18191, doi:10.1371/journal.pone.0018191.
Chai, Y. and Lin, Y.F. Stimulation of neuronal KATP channels by cGMP-dependent protein kinase: Involvement of ROS and 5-hydroxydecanoate-sensitive factors in signal transduction. Am. J. Physiol. Cell Physiol., 2010 Apr;298: C875-C892. Epub 2010 Jan 6.
Chen, T.Y., Lin, Y.F. and Zheng, J. Electrophysiological measurements of membrane proteins, T. Jue (ed), Fundamental Concepts in Biophysics, Vol. 1, Series: Handbook of Modern Biophysics, 2009 Jan; Humana Press, Totowa, NJ.
Chai, Y. and Lin, Y.F. Dual regulation of the ATP-sensitive potassium channel by activation of cyclic GMP-dependent protein kinase. Pflügers Arch.-European J. Physiol. 2008 Aug;456: 897-915. Epub 2008 Jan 30.
Lin, Y.F. and Chai, Y. Modulation of the ATP-sensitive potassium channel by extracellular signal-regulated kinase-mediated phosphorylation. Neuroscience 2008 Mar 18;152: 371-380. Epub 2008 Jan 9.
Misaki, N., Mao, X., Lin, Y.F., Suga, S., Li, G.H., Liu, Q., Chang, Y., Wang, H, Wakui, M. and Wu, J. Iptakalim, a vascular KATP channel opener, closes rat pancreatic beta-cell KATP channels and increases insulin release. J. Pharmacol. Exp. Ther. 2007 Aug;322: 871-878. Epub 2007 May 23.
Mao, X., Chai, Y. and Lin, Y.F. Dual regulation of ATP-sensitive potassium channels by caffeine. Am. J. Physiol. Cell Physiol. 2007 Jun;292: C2239-C2258. Epub 2007 Feb 15.
Lin, Y.F.*, Raab-Graham, K., Jan, Y.N. and Jan, L.Y. Nitric oxide stimulation of ATP-sensitive potassium channels: Involvement of Ras/MAPK kinase pathway and contribution to neuroprotection. Proc. Natl. Acad. Sci. USA 2004 May 18;101: 7799-7804. (* as corresponding author)
Bichet, D., Lin, Y.F., Ibarra, C.A., Huang, C.S., Yi, B.A., Jan, Y.N. and Jan, L.Y. Evolving potassium channels via yeast selection reveals structural elements important for selectivity. Proc. Natl. Acad. Sci. USA 2004 Mar 30;101: 4441-4446.
Yi, B.A., Minor, D.L., Lin, Y.F., Jan, Y.N. and Jan, L.Y. Controlling potassium channel activities: interplay between the membrane and intracellular factors. Proc. Natl. Acad. Sci. USA 2001 Sep 25;98: 11016-11023.
Yi, B.A., Lin, Y.F., Jan, Y.N. and Jan, L.Y. Yeast screen for constitutively active mutant G protein-activated potassium channels. Neuron 2001 Mar;29: 657-667.
Ma, D., Zerangue, N., Lin. Y.F., Collins, A., Yu, M., Jan, Y.N. and Jan, L.Y. Role of ER export signals in controlling surface potassium channel numbers. Science 2001 Jan 12;291: 316-319.
Minor, D.L., Lin, Y.F., Mobley, B.C., Avelar, A., Jan, Y.N., Jan, L.Y. and Berger, J.M. The polar T1 interface is linked to conformational changes that open the voltage-gated potassium channel. Cell 2000 Sep 1;102: 657-670.
Lin, Y.F., Jan, Y.N. and Jan, L.Y. Regulation of ATP-sensitive potassium channel function by protein kinase A-mediated phosphorylation in transfected HEK293 cell. EMBO J. 2000 Mar 1;19: 942-955.
Lin, Y.F., Angelotti, T.P., Dudek, E.M., Browning, M.D. and Macdonald, R.L. Protein kinase C phosphorylation of the Alpha 1 and Beta 2 gamma subunits of the GABAA receptor enhances whole-cell currents expressed in L929 fibroblasts. Mol. Pharmacol. 1996;50: 185-195.
Lin, Y.F., Browning, M.D., Dudek, E.M. and Macdonald, R.L. Protein kinase C enhances bovine Alpha 1 Beta 1 Gamma 2L GABAA receptor whole-cell currents expressed in L929 fibroblasts. Neuron 1994;13: 1421-1431.
Chai, C.Y., Wu, W.C., Wang, S., Su, C.K., Lin, Y.F., Yen, C.T., Kuo, J.S. and Wayner, M.J. Coexistence of autonomic and somatic mechanisms in the pressor areas of medulla in cats. Brain Res. Bull. 1992 Jul;29: 15-26.
Yen, C.T., Hwang, J.C., Su, C.K., Lin, Y.F., Yang, J.M. and Chai, C.Y. Differential actions of the median region of caudal medulla on autonomic nerve activities. Clin. Exp. Pharmacol. Physiol. 1991 Nov;18: 743-751.
Chai, C.Y., Lin, Y.F., Wang, H.Y., Wu, W.C., Yen, C.T., Kuo, J.S. and Wayner, M.J. Inhibition of spinal reflexes by paramedian reticular nucleus. Brain Res. Bull. 1990 Oct;25: 581-588.
- Lothman Fellowship
- University of California Davis, Health System Research Award
- Harrison Endowed Chair in Diabetes Research Award
- American Heart Association Scientist Development Award (National Center)
- University of California Davis, Research Insurance Grant to Promote Extramural Funding
- American Physiological Society Travel Award
- University of California Davis, Genome Center Proteomics Core Faculty Pilot Project
- MCP 210A: Advanced Physiology (graduate course)
- HPH 400: Medical Physiology
- PTX 202: Principles of Pharmacology and Toxicology--Cellular and Molecular Basis of Drug Action (graduate course)
- HPH493/SUR493: Special Study Module for M4 students: Care of Critically Ill Surgical
- Patient: Use of Physiological Principles
- American Heart Association, National Center
- UC Davis Academic Senate
- UC Davis Health System