Fundamentals

History of ion channels

BY      |     January 13, 2020

Before the 1660s the Theory of Animal Spirits dominated thinking regarding the function of the nervous system. “Animal spirits” (originating in the brain) were believed to control movements of the body by flowing through the nerves into the muscles.

1660s

Dutch biologist and microscopist Jan Swammerdam developed an isolated nerve-muscle preparation and showed that “irritation” of the nerve triggered muscle contractions. Swammerdam’s experiments proved the Theory of Animal Spirits inconsistent and laid the foundations of modern electrophysiology.

1791

Italian biologist and physicist Luigi Galvani developed the theory of intrinsic “animal electricity”; compared muscle and nerve fibers to a Leiden jar, and therefore contemplated accumulation of positive and negative charges on the inner and outer surfaces of the fibers; demonstrated that electrical stimulus can induce muscle contraction; predicted the existence of water-filled holes allowing the current flow through the surface of muscle and nerve fibers.

1828

Italian physicist Leopoldo Nobili first measured animal electricity (“frog current”) with a galvanometer.

1838

Italian physicist Carlo Matteucci proved that Nobilli’s “frog current” had a purely biological origin and thus confirmed the existence of animal electricity. He also recorded a “muscle current” between injured and intact muscle tissue. 

1848

German physiologist Emil du Bois-Reymond measured nerve’s excitatory current (“action current”) and suggested that excitation decreased the potential difference between an intact and an injured surface of the tissue (“negative Schwankung”).

1850

German physiologist and physicist Hermann von Helmholtz determined the speed of the nerve impulse that provoked muscular contraction.

1868

German physiologist Julius Bernstein recorded resting and action potentials using his “differential rheotome”. He determined that at rest, the potential of the nerve interior is about 60mV more negative with respect to the outside.

1879

German physiologist Ludimar Hermann proposed to study nerve impulse propagation by analogy with telegraph submarine cables. Proposed “local currents” hypothesis related to nerve impulse propagation.

1899

British physiologist Charles Ernest Overton introduced the concept of a lipid cell membrane.

1902

Julius Bernstein formulated his “Membrane Theory”: – cell membrane is selectively permeable to ions; – at rest, selective K+ permeability determines potential difference across the cell membrane; – during excitation membrane permeability to ions increases, leading to decrease in potential difference across the membrane.

1902

Charles Ernest Overton further developed Bernstein’s theory and suggested that extracellular Na+ is essential for excitability. He also proposed that nerve excitation and muscle contraction require a Na+/K+ exchange.

1925

Dutch physiologists Evert Gorter and François Grendel proposed the lipid bilayer structure of the cell plasma membrane.

1935

English physiologists Hugh Davson and James Frederic Danielli suggested that cell membranes are made of lipid bilayers with proteins. 

1936

English zoologist John Zachary Young introduced and characterized the structure of a squid giant axon.

1939

American biophysicists Kenneth Cole and Howard Curtis demonstrated a pronounced increase in membrane conductance with no changes in membrane capacitance during the action potential in a squid giant axon.

1939

English biophysicists Alan Hodgkin and Andrew Huxley as well as American biophysicists Kenneth Cole and Howard Curtis (1940) independently used intracellular microelectrodes to perform first direct measurements of action potentials in squid giant axons.

1949

American physiologists Gilbert Ling and Ralph Gerard developed a technique of preparing glass micropipette electrodes with a tip diameter <0.5microm.

1949

American biophysicists Kenneth Cole and George Marmont introduced the concepts of current clamp and voltage clamp.

1949

English biophysicists Alan Hodgkin and Bernard Katz demonstrated the importance of extracellular Na+ for action potentials.

1952

English biophysicists Alan Hodgkin and Andrew Huxley described the ionic mechanisms underlying the initiation and propagation of action potentials. They also developed a quantitative model for action potential generation. These findings are considered to be a central pillar of modern neuroscience research.

1955

English biophysicists Alan Hodgkin and Richard Keynes proposed that K+ ions cross the membrane coordinately through narrow tubes or channels and not by free diffusion.

1961

American biophysicist Alfred Strickholm used fire-polished glass pipettes to perform impedance and current recordings from a small electrically isolated area of the muscle cell surface.

1963

American biophysicist Karl Frank and French neuroscientist Ladislav Tauc recorded currents from electrically isolated membrane areas on molluscan neurons.

1963

The Nobel Prize in Physiology or Medicine was awarded jointly to Alan Hodgkin, Andrew Huxley and John Eccles “for their discoveries concerning the ionic mechanisms involved in excitation and inhibition in the peripheral and central portions of the nerve cell membrane.”

1960s-1970s

American scientists Clay Armstrong, Bertil Hille and Francisco Bezanilla introduced and developed the concept of ion channels as aqueous pores made of protein. They coined such widely used terms as selectivity filter, voltage sensor, gating, inner and outer vestibules, and gating current.

1969

German scientists Erwin Neher and Hans Dieter Lux for the first time applied gentle suction to the pipette interior in order to improve the contact between the pipette and the cell membrane during extracellular recordings.

1970

American scientists Stephen Hladky and Denis Haydon performed first gramicidin single-channel recordings in the lipid bilayer.

1972

American cell biologist Seymour Jonathan Singer and biochemist Garth Nicolson introduced Fluid Mosaic Model of cell membrane.

1976

German scientists Erwin Neher and Bert Sakmann developed the patch-clamp technique and performed first recordings of acetylcholine receptor single-channel currents from the membrane of denervated frog muscle fibers.

1980

Frederick Sigworth and Erwin Neher introduced the concept of a “giga-seal”.

1981

Owen Hamill, Alain Marty, Erwin Neher, Bert Sakmann and Frederick Sigworth introduced improved patch-clamp technique used till now as a gold standard technique to study ion channel function.

1984

Cloning of a sodium channel from an electric eel by Masaharu Noda et al.

1987

Cloning of a calcium channel from rabbit skeletal muscle by Tsutomu Tanabe et al.

1987

Cloning of the Shaker potassium channel from Drosophila melanogaster by Alexander Kamb et al. and Bruce Tempel et al.

1991

Erwin Neher and Bert Sakmann have been awarded The Nobel Prize in Physiology or Medicine “for their discoveries concerning the function of single ion channels in cells.”

Late 1990s

Development of first automated patch clamp systems.

1998

American scientist Roderick MacKinnon and collaborators published the first crystal structure of an ion channel – the bacterial potassium channel KcsA.

2003

Roderick MacKinnon and Peter Agre have been awarded The Nobel Prize in Chemistry “for structural and mechanistic studies of ion channels” and “for the discovery of water channels”, respectively.

Late 1990s-2000s

Multiple discoveries of new ion channel types.


Image from Wellcome Collection. CC BY


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