ErwinNeherandBertSakmann.in1976,ErwinNeherandBertSakmannpressedasmoothelectrodetip onthe surface of an isolated skeletal musclefiber,electricallyisolatingapatchofmembraneandreducingextraneous electricalnoise so lowthatpicoampere currentsflowingthroughasingle ion channelcouldbe measureddirectlyThepatchclamptechniquewasborn,and it quicklybecamethebackbone of modernelectrophysiology.Ithassincebeenreferred to as the singlemost importantdevelopmentinionchannelresearchinthelasthalfofthetwentieth century.In1991,NeherandSackmannwererewardedtheNobelPrizefor Physiology or Medicinefor the development ofthepatchclamptechnique
Erwin Neher and Bert Sakmann in 1976, Erwin Neher and Bert Sakmann pressed a smooth electrode tip on the surface of an isolated skeletal muscle fiber, electrically isolating a patch of membrane and reducing extraneous electrical noise so low that picoampere currents flowing through a single ion channel could be measured directly. The patch clamp technique was born, and it quickly became the backbone of modern electrophysiology. It has since been referred to as the single most important development in ion channel research in the last half of the twentieth century. In 1991, Neher and Sackmann were rewarded the Nobel Prize for Physiology or Medicine for the development of the patch clamp technique
NobelPrize-lonchannels1991 Functionof singleionchannelsincellsNeher,Erwin3/20/1944toGermanSakmann,Bert6/12/1942toGerman
Nobel Prize – Ion channels 1991 Function of single ion channels in cells Neher, Erwin 3/20/1944 to German Sakmann, Bert 6/12/1942 to German
BreakthroughsinotherscientificareasClayArmstrongin1973proposedthatthestructureofsodiumchannels in the squid neuron allows for opening and closing oftheirpores bya“balland chain"model.Theadvent of recombinantDNAtechnology inthemid to late1970s providedthe meansforobtaining sequenceinformationabout genes,proteins.With the amino acid sequences known, itwaspossibletobegin predictions of what ion channelsshouldlooklike inthree-dimensional space.The sequence couldbechanged deliberately(site-directed mutagenesis)in ordertounderstandhowitworked.Cloningofthefirstionchannel(nicotinicacetylcholine receptornAChR)occurredin1982,andthefirstchanneltobesequencedwasthe Natchannel,followed bythe Ca2+ channel.Soonthereafter,thefirstK+channelwascharacterized
Breakthroughs in other scientific areas Clay Armstrong in 1973 proposed that the structure of sodium channels in the squid neuron allows for opening and closing of their pores by a “ball and chain” model. The advent of recombinant DNA technology in the mid to late 1970s provided the means for obtaining sequence information about genes, proteins. With the amino acid sequences known, it was possible to begin predictions of what ion channels should look like in three-dimensional space. The sequence could be changed deliberately (site-directed mutagenesis) in order to understand how it worked. Cloning of the first ion channel (nicotinic acetylcholine receptor, nAChR) occurred in 1982, and the first channel to be sequenced was the Na+ channel, followed by the Ca2+ channel. Soon thereafter, the first K+ channel was characterized
Breakthroughsin otherscientific areasIntroduction ofrecombinantexpressionofionchannelsprovided a well-defined, replenishable source of cellsexpressingavariety ofhumanion channels,openingthewaytoanumberofbiochemicalassaystostudyionchannelfunctionThereis littledoubtthat combiningtheinformationandknowledgeacquiredfromelectrophysiology,molecularbiology,crystallography,and othertechniqueshasgreatly improved the understanding of ion channelstructure and function, and heightened the interest indeveloping novelion channelmodulators
Breakthroughs in other scientific areas Introduction of recombinant expression of ion channels provided a well-defined, replenishable source of cells expressing a variety of human ion channels, opening the way to a number of biochemical assays to study ion channel function. There is little doubt that combining the information and knowledge acquired from electrophysiology, molecular biology, crystallography, and other techniques has greatly improved the understanding of ion channel structure and function, and heightened the interest in developing novel ion channel modulators
RoderickMacKinnonThefirst highresolution crystal structure of an ion channel(3.2A resolution),the potassium channel KscA fromabacteria,wasprovidedby MacKinnonand hisgroup.Thismeant that it was possible to determine the exact positionsof nearlyall of the individual atoms in the proteinHis work revealed forthe firsttimethe inner workingsof anionchannel atthe atomiclevel.Itprovidedtremendousinsight into theselectivity of potassium channelsbyrevealing ringsofcarboxyl oxygenatomsinthe narrowselectivity filter that stabilizethe potassium ions as theytravel in the water-filled cavity in the center of the channelandshedtheirwatermolecules.Forthisastonishingbreakthrough,MacKinnonwasawardedtheNobel PrizeinChemistryin2003
Roderick MacKinnon The first high resolution crystal structure of an ion channel (3.2Å resolution), the potassium channel KscA from a bacteria, was provided by MacKinnon and his group. This meant that it was possible to determine the exact positions of nearly all of the individual atoms in the protein. His work revealed for the first time the inner workings of an ion channel at the atomic level. It provided tremendous insight into the selectivity of potassium channels by revealing rings of carboxyl oxygen atoms in the narrow selectivity filter that stabilize the potassium ions as they travel in the water-filled cavity in the center of the channel, and shed their water molecules. For this astonishing breakthrough, MacKinnon was awarded the Nobel Prize in Chemistry in 2003