Bertil Hille

Last updated
Bertil Hille
Born(1940-10-10)October 10, 1940
NationalityAmerican
Alma mater Yale University, The Rockefeller University
SpouseMerrill Burr Hille
Awards Louisa Gross Horwitz Prize, Albert Lasker Award, Gairdner Foundation International Award
Scientific career
Fields Ion channels
Institutions University of Washington

Bertil Hille (born October 10, 1940) is an Emeritus Professor, and the Wayne E. Crill Endowed Professor in the Department of Physiology and Biophysics at the University of Washington. [1] He is particularly well known for his pioneering research on cell signalling by ion channels. His book Ion Channels of Excitable Membranes has been the standard work on the subject, appearing in multiple editions since its first publication in 1984. [2]

Contents

Biography

Early life and education

Hille was born in New Haven, Connecticut. His father is Carl Einar Hille, a Yale math professor and a member of the U.S. National Academy of Sciences and the Royal Swedish Academy of Sciences. He attended the Foote School and Westminster School (Connecticut). [3]

Hille received his B.S. summa cum laude in Zoology from Yale University (1962) and his Ph.D. in Life Sciences from The Rockefeller University (1967). During his PhD, Hille started his long-term collaboration with Clay Armstrong, who he shared many awards with several decades later. After completing his Ph.D, Hille did postdoc research with Sir Alan L. Hodgkin (1963 Nobel laureate for the basis of nerve action potentials) and Richard Keynes at the University of Cambridge, England. [4]

Career

In 1968 Hille joined the Department of Physiology and Biophysics at the University of Washington's School of Medicine. In 2005, he was named the Wayne E. Crill Endowed Professor. On July 1, 2021, he became a professor emeritus. [5]

Personal life

Bertil Hille is married to Merrill Burr Hille, Professor Emerita of Biology at the University of Washington, and has two sons, Erik Darwin Hille and Jon Trygve Hille Grey. [3]

Scientific contributions

Bertil Hille pioneered the concept of ion channels as membrane proteins forming gated aqueous pores (with Clay Armstrong). [6] [7] He showed that Na+ and K+ channels of axons could be distinguished by drugs such as tetrodotoxin and tetraethylammonium ion, and that their ionic selectivity can be understood by limiting pore size, the selectivity filter, and by movements of ions through a series of saturable sites. He showed that local anesthetics enter Na+ channels in a state-dependent manner. [3] [8] [9]

In 1984, Hille started a new direction of studying the modulation of ion channels by G protein–coupled receptors. He distinguished two new signaling pathways for excitable cells. A fast, pertussis toxin-sensitive pathway turned on inward rectifier K+ channels and turned off Ca2+ channels by G protein Gβγ subunits. A slow, pertussis toxin-insensitive pathway turned off some K+ and Ca2+ channels by depleting the plasma membrane phosphoinositides, phosphatidylinositol 4,5-bisphosphate (PIP2). New tools and findings from the Hille lab, together with the initial finding (1996) from Donald W. Hilgemann's lab at UT southwestern, demonstrated that PIP2 is an essential cofactor for many ion channels and transporters. The low-abundance signaling lipid PIP2 indeed plays a significant role in regulating neuronal and cardiac excitability. Hille has developed a detailed model of the PIP2 loss mechanism and its effects on the muscarinic inhibition of M-channels. [10] [9]

Hille has published more than 200 papers and book chapters. [5] He is the author of multiple editions of Ion Channels of Excitable Membranes, described as an essential introduction not just for beginners but for readers throughout the areas of biochemistry and biophysics. Hille's book is considered to mark a turning point in the field, [2] [11] defining the modern era of ion channel studies. [12] The book is known for its clarity of language, [13] its ability to communicate to both the beginner and the specialist, [14] its attention to research history, and the breadth and depth of its scientific coverage. [12]

Awards and distinctions

Related Research Articles

<span class="mw-page-title-main">Ion channel</span> Pore-forming membrane protein

Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophoric proteins, the other being ion transporters.

<span class="mw-page-title-main">Action potential</span> Neuron communication by electric impulses

An action potential occurs when the membrane potential of a specific cell rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of excitable cells, which include animal cells like neurons and muscle cells, as well as some plant cells. Certain endocrine cells such as pancreatic beta cells, and certain cells of the anterior pituitary gland are also excitable cells.

<span class="mw-page-title-main">Bert Sakmann</span> German Nobel laureate

Bert Sakmann is a German cell physiologist. He shared the Nobel Prize in Physiology or Medicine with Erwin Neher in 1991 for their work on "the function of single ion channels in cells," and the invention of the patch clamp. Bert Sakmann was Professor at Heidelberg University and is an Emeritus Scientific Member of the Max Planck Institute for Medical Research in Heidelberg, Germany. Since 2008 he leads an emeritus research group at the Max Planck Institute of Neurobiology.

<span class="mw-page-title-main">Erwin Neher</span> German biophysicist and Nobel laureate

Erwin Neher is a German biophysicist, specializing in the field of cell physiology. For significant contribution in the field, in 1991 he was awarded, along with Bert Sakmann, the Nobel Prize in Physiology or Medicine for "their discoveries concerning the function of single ion channels in cells".

<span class="mw-page-title-main">Roderick MacKinnon</span> American biophysicist, neuroscientist, and businessman

Roderick MacKinnon is an American biophysicist, neuroscientist, and businessman. He is a professor of molecular neurobiology and biophysics at Rockefeller University who won the Nobel Prize in Chemistry together with Peter Agre in 2003 for his work on the structure and operation of ion channels.

<span class="mw-page-title-main">Potassium channel</span> Ion channel that selectively passes K+

Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of cell functions.

<span class="mw-page-title-main">Voltage-gated ion channel</span> Type of ion channel transmembrane protein

Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in the electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins, regulating their opening and closing. Cell membranes are generally impermeable to ions, thus they must diffuse through the membrane through transmembrane protein channels. They have a crucial role in excitable cells such as neuronal and muscle tissues, allowing a rapid and co-ordinated depolarization in response to triggering voltage change. Found along the axon and at the synapse, voltage-gated ion channels directionally propagate electrical signals. Voltage-gated ion-channels are usually ion-specific, and channels specific to sodium (Na+), potassium (K+), calcium (Ca2+), and chloride (Cl) ions have been identified. The opening and closing of the channels are triggered by changing ion concentration, and hence charge gradient, between the sides of the cell membrane.

Phosphatidic acids are anionic phospholipids important to cell signaling and direct activation of lipid-gated ion channels. Hydrolysis of phosphatidic acid gives rise to one molecule each of glycerol and phosphoric acid and two molecules of fatty acids. They constitute about 0.25% of phospholipids in the bilayer.

<span class="mw-page-title-main">Randy Schekman</span> American cell biologist

Randy Wayne Schekman is an American cell biologist at the University of California, Berkeley, former editor-in-chief of Proceedings of the National Academy of Sciences and former editor of Annual Review of Cell and Developmental Biology. In 2011, he was announced as the editor of eLife, a new high-profile open-access journal published by the Howard Hughes Medical Institute, the Max Planck Society and the Wellcome Trust launching in 2012. He was elected to the National Academy of Sciences in 1992. Schekman shared the 2013 Nobel Prize for Physiology or Medicine with James Rothman and Thomas C. Südhof for their ground-breaking work on cell membrane vesicle trafficking.

<span class="mw-page-title-main">Inward-rectifier potassium channel</span> Group of transmembrane proteins that passively transport potassium ions

Inward-rectifier potassium channels (Kir, IRK) are a specific lipid-gated subset of potassium channels. To date, seven subfamilies have been identified in various mammalian cell types, plants, and bacteria. They are activated by phosphatidylinositol 4,5-bisphosphate (PIP2). The malfunction of the channels has been implicated in several diseases. IRK channels possess a pore domain, homologous to that of voltage-gated ion channels, and flanking transmembrane segments (TMSs). They may exist in the membrane as homo- or heterooligomers and each monomer possesses between 2 and 4 TMSs. In terms of function, these proteins transport potassium (K+), with a greater tendency for K+ uptake than K+ export. The process of inward-rectification was discovered by Denis Noble in cardiac muscle cells in 1960s and by Richard Adrian and Alan Hodgkin in 1970 in skeletal muscle cells.

Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels.

Clay Margrave Armstrong is an American physiologist and a former student of Andrew Fielding Huxley. Armstrong received his MD from Washington University School of Medicine in 1960. He is currently emeritus professor of physiology at the University of Pennsylvania. He has also held professorial appointments at Duke University and the University of Rochester.

Sir Michael John Berridge (22 October 1938 - 13 February 2020) was a British physiologist and biochemist. He was known for his work on cell signaling, in particular the discovery that inositol trisphosphate acts as a second messenger, linking events at the plasma membrane with the release of calcium ions (Ca2+) within the cell.

<span class="mw-page-title-main">Julius Bernstein</span> German physiologist

Julius Bernstein was a German physiologist born in Berlin. His father was Aron Bernstein (1812–1884), a founder of the Reform Judaism Congregation in Berlin 1845; his son was the mathematician Felix Bernstein (1878–1956).

<span class="mw-page-title-main">Gating (electrophysiology)</span>

In electrophysiology, the term gating refers to the opening (activation) or closing of ion channels. This change in conformation is a response to changes in transmembrane voltage.

Boris Khodorov was a Soviet and Russian physiologist, M.D., D.Sc., professor of physiology, and head of the Cell Physiology section of Moscow Physiological Society.

Clara Franzini-Armstrong is an Italian-born American electron microscopist, and Professor Emeritus of Cell and Developmental Biology at University of Pennsylvania.

M current is a type of noninactivating potassium current first discovered in bullfrog sympathetic ganglion cells.

<span class="mw-page-title-main">Peter Hegemann</span> German biophysicist

Peter Hegemann is a Hertie Senior Research Chair for Neurosciences and a professor of Experimental Biophysics at the Department of Biology, Faculty of Life Sciences, Humboldt University of Berlin, Germany. He is known for his discovery of channelrhodopsin, a type of ion channels regulated by light, thereby serving as a light sensor. This created the field of optogenetics, a technique that controls the activities of specific neurons by applying light. He has received numerous accolades, including the Rumford Prize, the Shaw Prize in Life Science and Medicine, and the Albert Lasker Award for Basic Medical Research.

Sarah K. England is a physiologist and biophysicist and the Alan A. and Edith L. Wolff Professor of Obstetrics and Gynaecology at Washington University School of Medicine. England conducts research on cation channels in uterine smooth muscle to understand the biological correlates of preterm birth and is the Associate Program Director of the Prematurity Research Center at Washington University as well as the Vice Chair of Research for the Center for Reproductive Health Sciences. In 2005, England was selected as a Robert Wood Johnson Foundation Health Policy Fellow in the Office of Senator Hillary Clinton where she used her scientific expertise in obstetrics and gynaecology to guide policy changes.

References

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