Bertil Hille

powered by
COS Expertise®
University of Washington
School of Medicine
Physiology and Biophysics
ProfessorAppointed: 1968
Professional Headshot of Bertil Hille

Mailing Address

Physiology and Biophysics
University of Washington Sch Med
Box 357290
Seattle, Washington 98195-7290
United States

Contact Information

Phone: (206) 543-8639
Fax: (206) 685-0619
hille@u.washington.edu

Qualifications

Ph.D., The Rockefeller University, 1967.

Expertise and Research Interests

We are interested in cell signaling by ion channels, neurotransmitters and hormones acting through G-protein coupled receptors, second messengers, intracellular calcium, and exocytosis. Our overall goal is to define each step and the molecular mechanisms underlying physiologically interesting activation and inhibition in single cells, with emphasis on events that occur in time scales of microseconds to seconds. Our approach is biophysical and quantitative.

The cell membrane, cytoplasm and intracellular organelles form a rapidly interacting signaling network. We study single neurons, endocrine cells, epithelia, sperm, and cell lines using techniques associated with the patch clamp: voltage clamp, membrane capacitance, optical imaging, photometry of fluorescent dyes, and amperometry. We have analysed G-protein coupled modulation of neuronal Ca channels, responses of gonadotropes and somatotropes to their releasing hormones, vesicular exocytosis and secretion in excitable cells and in epithelial cells, dynamics of intraorganellar calcium in chromaffin cells and gonadotropes, and calcium signals, calcium channels, and regulation of flagellar beating and calcium entry in sperm.

Keywords

COS Keywords:

Biophysics, Cell Biology, Cell Physiology, Endocrine System, Endocrinology, Hormones, Ion Channels, Membrane Transport, Nervous System, Neurobiology, Neurons, Neurotransmitters, Physiology, Receptors, Reproductive Biology.

Additional Terms:

Calcium in the Regulation of Tissue, Cell Biology, Cell-Cell Interactions, Endocrinology, G Proteins, G-protein Coupled Receptors, Ion Channels, Membrane Transport, Nervous System, Neurobiology, Neurons, PIP2, Phosphoinositides, Phospholipase C, Receptors, Reproductive Biology, Spermatozoa, Transmitters.

Memberships

American Association for the Advancement of Science
Biophysical Society
Physiological Society
Society for Neuroscience

Honors and Awards

2002, Member of Academy of Medicine,
2001, Gairdner International Award, Gairdner Foundation, Canada, Medical Science, Shared with Rod MacKinnon and Clay Armstrong
1999, The Albert Lasker Basic Medical Research Award (with Clay Armstrong and Roderick MacKinnon),
1998, Fellow of American Academy of Arts and Sciences,
1996, Louisa Gross Horwitz Prize for Biology or Biochemistry, shared with Dr. Clay Armstrong, Columbia University
1986, Member of National Academy of Sciences USA,

Previous Positions

1971-1974, Associate Professor, University of Washington, School of Medicine, Physiology and Biophysics
1968-1971, Assistant Professor, University of Washington, School of Medicine, Physiology and Biophysics

Publications

  • Carlson AE, Quill TA, Westenbroek RE, Schuh SM, Hille B, Babcock DF (Sep 2005) Identical phenotypes of CatSper1 and CatSper2 null sperm., The Journal of Biological Chemistry, 280 (37), 32238-44 Abstract
  • Horowitz LF, Hirdes W, Suh BC, Hilgemann DW, Mackie K, Hille B (Sep 2005) Phospholipase C in living cells: activation, inhibition, Ca2+ requirement,, The Journal of General Physiology, 126 (3), 243-62 Abstract
  • Suh BC, Hille B (Jun 2005) Regulation of ion channels by phosphatidylinositol 4,5-bisphosphate., Current Opinion in Neurobiology, 15 (3), 370-8 Abstract
  • Hirdes W, Horowitz LF, Hille B (Aug 2004) Muscarinic modulation of erg potassium current., The Journal of Physiology, 559 (Pt 1), 67-84 Abstract
  • Suh BC, Horowitz LF, Hirdes W, Mackie K, Hille B (Jun 2004) Regulation of KCNQ2/KCNQ3 current by G protein cycling: the kinetics of receptor-mediated signaling by Gq., The Journal of General Physiology, 123 (6), 663-83 Abstract
  • Jung SR, Kim MH, Hille B, Nguyen TD, Koh DS (Mar 2004) Regulation of exocytosis by purinergic receptors in pancreatic duct epithelial cells., American Journal of Physiology. Cell Physiology, 286 (3), C573-9 Abstract
  • Carlson AE, Westenbroek RE, Quill T, Ren D, Clapham DE, Hille B, Garbers DL, Babcock DF (Dec 2003) CatSper1 required for evoked Ca2+ entry and control of flagellar function in sperm., Proceedings of the National Academy of Sciences of the United States of America., 100 (25), 14864-8 Abstract
  • Chen L, Koh DS, Hille B, Dynamics of calcium clearance in mouse pancreatic beta-cells, Diabetes, 52(7), 1723-31, July 2003 Abstract
  • Wennemuth G, Babcock DF, Hille B (Jul 2003) Calcium clearance mechanisms of mouse sperm., The Journal of General Physiology, 122 (1), 115-28 Abstract
  • Zhu H, Hille B, Xu T, Sensitization of regulated exocytosis by protein kinase C, Proceedings of the National Academy of Sciences (USA), 99(26), 17055-9, December 2002 Abstract
  • Roche JP, Westenbroek R, Sorom AJ, Hille B, Mackie K, Shapiro MS, Antibodies and a cysteine-modifying reagent show correspondence of M current in neurons to KCNQ2 and KCNQ3 K+ channels, British Journal of Pharmacology, 137(8), 1173-86, December 2002 Abstract
  • Suh BC, Hille B, Recovery from muscarinic modulation of M current channels requires phosphatidylinositol 4,5-bisphosphate synthesis, Neuron, 35(3), 507-20, Aug 2002 Abstract
  • Bertil Hille, Ion Channels of Excitable Membranes, Sinauer Associates, 814 pp., 2001
  • Kim KT, Koh DS, Hille B, Loading of oxidizable transmitters into secretory vesicles permits carbon-fiber amperometry, Journal of Neuroscience, 20(20), RC101, 2000 Abstract
  • Koh DS, Moody MW, Nguyen TD, Hille B, Regulation of exocytosis by protein kinases and Ca(2+) in pancreatic duct epithelial cells, Journal of General Physiology, 116(4), 507-20, October 2000 Abstract
  • Kaftan EJ, Xu T, Abercrombie RF, Hille B, Mitochondria shape hormonally induced cytoplasmic calcium oscillations and modulate exocytosis, Journal of Biological Chemistry, 275(33), 25465-70, August 2000 Abstract
  • Wennemuth G, Westenbroek RE, Xu T, Hille B, Babcock DF, CaV2.2 and CaV2.3 (N- and R-type) Ca2+ channels in depolarization-evoked entry of Ca2+ into mouse sperm, Journal of Biological Chemistry, 275(28), 21210-7, July 2000 Abstract
  • Shapiro MS, Roche JP, Kaftan EJ, Cruzblanca H, Mackie K, Hille B, Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K(+\) channels that underlie the neuronal M current., Journal of Neuroscience, 20(5), 1710-21, 1 2000 Abstract
  • Hille B, Billiard J, Babcock DF, Nguyen T, Koh DS, Stimulation of exocytosis without a calcium signal, Journal of Physiology, 520 Pt 1, 23-31, October 1999 Abstract
  • Hille B, Armstrong CM, MacKinnon R, Ion channels: from idea to reality, Nature Medicine, 5(10), 1105-9, October 1999 Abstract
  • Shapiro MS, Loose MD, Hamilton SE, Nathanson NM, Gomeza J, Wess J, Hille B, Assignment of muscarinic receptor subtypes mediating G-protein modulation of Ca\(2+\) channels by using knockout mice., Proceedings of the National Academy of Sciences (USA), 96(19), 10899-904, 14 Sep 1999 Abstract
  • Koh DS, Hille B, Rapid fabrication of plastic-insulated carbon-fiber electrodes for micro-amperometry., Journal of Neuroscience Methods, 88(1), 83-91, 1 Apr 1999 Abstract
  • Cruzblanca H, Koh D S, Hille B, Bradykinin inhibits M current via phospholipase C and Ca2+ release from IP3-sensitive Ca2+ stores in rat sympathetic neurons., Proceedings of the National Academy of Sciences (USA), 95(12), 7151-6, 9 Jun 1998 Abstract
  • Babcock D F, Hille B, Mitochondrial oversight of cellular Ca2+ signaling., Current Opinion In Neurobiology, 8(3), 398-404, June 1998 Abstract
  • Garcia D E, Brown S, Hille B, Mackie K, Protein kinase C disrupts cannabinoid actions by phosphorylation of the CB1 cannabinoid receptor., Journal of Neuroscience, 18(8), 2834-41, 15 Apr 1998 Abstract
  • Armstrong CM, Hille B, Voltage-gated ion channels and electrical excitability, Neuron, 20(3), 371-80, March 1998 Abstract
  • Hamilton S E, Loose M D, Qi M, Levey A I, Hille B, McKnight G S, Idzerda R L, Nathanson N M, Disruption of the m1 receptor gene ablates muscarinic receptor-dependent M current regulation and seizure activity in mice., Proceedings of the National Academy of Sciences (USA), 94(24), 13311-6, 25 Nov 1997 Abstract
  • Billiard J, Koh D S, Babcock D F, Hille B, Protein kinase C as a signal for exocytosis., Proceedings of the National Academy of Sciences (USA), 94(22), 12192-7, 28 Oct 1997 Abstract
  • Zhou J, Shapiro M S, Hille B, Speed of Ca2+ channel modulation by neurotransmitters in rat sympathetic neurons., Journal of Neurophysiology, 77(4), 2040-8, April 1997 Abstract
  • Babcock D F, Herrington J, Goodwin P C, Park Y B, Hille B, Mitochondrial participation in the intracellular Ca2+ network., Journal of Cell Biology, 136(4), 833-44, 24 Feb 1997 Abstract
  • Koh D S, Hille B, Modulation by neurotransmitters of catecholamine secretion from sympathetic ganglion neurons detected by amperometry., Proceedings of the National Academy of Sciences (USA), 94(4), 1506-11, 18 Feb 1997 Abstract
  • Isaacson J S, Hille B, GABA(B)-mediated presynaptic inhibition of excitatory transmission and synaptic vesicle dynamics in cultured hippocampal neurons., Neuron, 18(1), 143-52, January 1997 Abstract
  • Nguyen T D, Koh D S, Moody M W, Fox N R, Savard C E, Kuver R, Hille B, Lee S P, Characterization of two distinct chloride channels in cultured dog pancreatic duct epithelial cells., American Journal of Physiology, 272(1 Pt 1), G172-80, January 1997 Abstract
  • Tse F W, Tse A, Hille B, Horstmann H, Almers W, Local Ca2+ release from internal stores controls exocytosis in pituitary gonadotrophs., Neuron, 18(1), 121-32, January 1997 Abstract
  • Hehl S, Golard A, Hille B, Involvement of mitochondria in intracellular calcium sequestration by rat gonadotropes., Cell Calcium, 20(6), 515-24, December 1996 Abstract
  • Shapiro M S, Zhou J, Hille B, Selective disruption by protein kinases of G-protein-mediated Ca2+ channel modulation., Journal of Neurophysiology, 76(1), 311-20, July 1996 Abstract
  • Park Y B, Herrington J, Babcock D F, Hille B, Ca2+ clearance mechanisms in isolated rat adrenal chromaffin cells., Journal of Physiology, 492 ( Pt 2), 329-46, 15 Apr 1996 Abstract
  • Herlitze S, Garcia D E, Mackie K, Hille B, Scheuer T, Catterall W A, Modulation of Ca2+ channels by G-protein beta gamma subunits., Nature, 380(6571), 258-62, 21 Mar 1996 Abstract
  • Herrington J, Park Y B, Babcock D F, Hille B, Dominant role of mitochondria in clearance of large Ca2+ loads from rat adrenal chromaffin cells., Neuron, 16(1), 219-28, January 1996 Abstract
  • Tse A, Tse F W, Hille B, Modulation of Ca2+ oscillation and apamin-sensitive, Ca2+-activated K+ current in rat gonadotropes., Pflügers archiv. European Journal of Physiology, 430(5), 645-52, September 1995 Abstract
  • Wollmuth L P, Shapiro M S, Hille B, Pancreatic polypeptide inhibits calcium channels in rat sympathetic neurons via two signaling pathways., Journal of Neurophysiology, 73(3), 1323-8, March 1995 Abstract
  • Hille B, Tse A, Tse F W, Bosma M M, Signaling mechanisms during the response of pituitary gonadotropes to GnRH., Recent Progress In Hormone Research, 50, 75-95, 1995 Abstract
  • Hille B, Beech DJ, Bernheim L, Mathie A, Shapiro MS, Wollmuth LP, Multiple G-protein-coupled pathways inhibit N-type Ca channels of neurons., Life Sciences, 56(11-12), 989-92, 1995 Abstract
  • Hille B, Modulation of ion-channel function by G-protein-coupled receptors., Trends In Neurosciences, 17(12), 531-6, December 1994 Abstract
  • Shapiro M S, Wollmuth L P, Hille B, Modulation of Ca2+ channels by PTX-sensitive G-proteins is blocked by N-ethylmaleimide in rat sympathetic neurons., Journal of Neuroscience, 14(11 Pt 2), 7109-16, November 1994 Abstract
  • Tse F W, Tse A, Hille B, Cyclic Ca2+ changes in intracellular stores of gonadotropes during gonadotropin-releasing hormone-stimulated Ca2+ oscillations., Proceedings of the National Academy of Sciences (USA), 91(21), 9750-4, 11 Oct 1994 Abstract
  • Herrington J, Hille B, Growth hormone-releasing hexapeptide elevates intracellular calcium in rat somatotropes by two mechanisms., Endocrinology, 135(3), 1100-8, September 1994 Abstract
  • Naumov A P, Herrington J, Hille B, Actions of growth-hormone-releasing hormone on rat pituitary cells: intracellular calcium and ionic currents., Pflügers archiv. European Journal of Physiology, 427(5-6), 414-21, July 1994 Abstract
  • Tse A, Tse F W, Hille B, Calcium homeostasis in identified rat gonadotrophs., Journal of Physiology, 477 ( Pt 3), 511-25, 15 Jun 1994 Abstract
  • Shapiro M S, Wollmuth L P, Hille B, Angiotensin II inhibits calcium and M current channels in rat sympathetic neurons via G proteins., Neuron, 12(6), 1319-29, June 1994 Abstract
  • Hille B, Tse A, Tse F W, Almers W, Calcium oscillations and exocytosis in pituitary gonadotropes., Annals of The New York Academy of Sciences, 710, 261-70, 9 Mar 1994 Abstract
  • Mackie K, Devane W A, Hille B, Anandamide, an endogenous cannabinoid, inhibits calcium currents as a partial agonist in N18 neuroblastoma cells., Molecular Pharmacology, 44(3), 498-503, September 1993 Abstract
  • Tse A, Tse F W, Almers W, Hille B, Rhythmic exocytosis stimulated by GnRH-induced calcium oscillations in rat gonadotropes., Science, 260(5104), 82-4, 2 Apr 1993 Abstract
  • Tse A, Hille B, Role of voltage-gated Na+ and Ca2+ channels in gonadotropin-releasing hormone-induced membrane potential changes in identified rat gonadotropes., Endocrinology, 132(4), 1475-81, April 1993 Abstract
  • Shapiro M S, Hille B, Substance P and somatostatin inhibit calcium channels in rat sympathetic neurons via different G protein pathways., Neuron, 10(1), 11-20, January 1993 Abstract
  • Wollmuth L P, Hille B, Ionic selectivity of Ih channels of rod photoreceptors in tiger salamanders., Journal of General Physiology, 100(5), 749-65, November 1992 Abstract
  • Bernheim L, Mathie A, Hille B, Characterization of muscarinic receptor subtypes inhibiting Ca2+ current and M current in rat sympathetic neurons., Proceedings of the National Academy of Sciences (USA), 89(20), 9544-8, 15 Oct 1992 Abstract
  • Hille B, G protein-coupled mechanisms and nervous signaling., Neuron, 9(2), 187-95, August 1992 Abstract
  • Mackie K, Hille B, Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells., Proceedings of the National Academy of Sciences (USA), 89(9), 3825-9, 1 May 1992 Abstract
  • Mathie A, Bernheim L, Hille B, Inhibition of N- and L-type calcium channels by muscarinic receptor activation in rat sympathetic neurons., Neuron, 8(5), 907-14, May 1992 Abstract
  • Yang J, Mathie A, Hille B, 5-HT3 receptor channels in dissociated rat superior cervical ganglion neurons., Journal of Physiology, 448, 237-56, March 1992 Abstract
  • Tse A, Hille B, GnRH-induced Ca2+ oscillations and rhythmic hyperpolarizations of pituitary gonadotropes., Science, 255(5043), 462-4, 24 Jan 1992 Abstract
  • Beech D J, Bernheim L, Hille B, Pertussis toxin and voltage dependence distinguish multiple pathways modulating calcium channels of rat sympathetic neurons., Neuron, 8(1), 97-106, January 1992 Abstract
  • Bernheim L, Beech D J, Hille B, A diffusible second messenger mediates one of the pathways coupling receptors to calcium channels in rat sympathetic neurons., Neuron, 6(6), 859-67, June 1991 Abstract
  • Beech D J, Bernheim L, Mathie A, Hille B, Intracellular Ca2+ buffers disrupt muscarinic suppression of Ca2+ current and M current in rat sympathetic neurons., Proceedings of the National Academy of Sciences (USA), 88(2), 652-6, 15 Jan 1991 Abstract

Profile Details

Last Verified: 7/5/2007

COS Expertise ID #307572
Reference this profile directly: http://myprofile.cos.com/BHille