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 Nobel laureate for the basis of nerve action potentials and Richard Keynes at the University of Cambridge , England. Scientific contributions[ edit ] Bertil Hille pioneered the concept of ion channels as membrane proteins forming gated aqueous pores with Clay Armstrong. In , Hille started a new direction of studying the modulation of ion channels by G protein—coupled receptors.
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Armstrong is a professor of physiology at the University of Pennsylvania in Philadelphia. Part 1: Ion Channels in Medicine and Biology "I think that ion channels are the most important single class of proteins that exist in the human body or any body for that matter," Dr. Armstrong tells a hypothetical skeptic from medical school.
We can follow it more or less closely, depending on how it evolves. I wanted to ask you a little bit about how you see the place of ion channels in biology and medicine and then ask you a little bit about your family background and your family today.
Then talk a little bit about your education and training in science—mainly the places and the people. And then really get into the meat of the science after that and talk about how you came to your wonderful insights into channel structure and function. And then the future. And then what you see the future of ion channel work being and what advice you might have for young people that are considering a career in science. Would that be reasonable?
That sounds fine. Suppose that a skeptical medical student came up to you and said, "Okay Dr. Armstrong I have too much to do. Why should I care about ion channels? And of course, the question is something like saying, "Which is the most important part of a car, the tires or the carburator?
But all of the higher functions, all of the communication between the parts of the body, depend very crucially on the function of ion channels, and every perception, for example, is encoded in electrical form through the function of ion channels. The heartbeat is another example. It is an electrical timing system dependent on ion channels that produces a heartbeat.
All of our thoughts, all of our motions involve the action of millions of ion channels—billions. Endocrine secretion. All of these are, of course, are in addition to the more basic functions of ion channels, which are involved in the very life of the cell—of every cell. No cell could exist without ion channels. So I regard it as extremely important and also medically important.
Well, epilepsy, for example, is one clear case. Myasthenia gravis is another. Various of the paralyses and myotonias. And so the channels also, I guess, are going to be very important, increasingly important drug targets for medical therapies of one kind and another.
And I would suppose that very large numbers of those must modify the action of ion channels in one way or another. Potassium channels are becoming clear targets of therapeutic intervention in, for example, diabetes and also in problems of arrhythmias of the heart. Thought, for example. Well, nobody knows in any precise detail how thought occurs, but that thought involves the use of ion channels seems very clear since all communication between cells and all communication within cells depends on ion channels.
The medical schools are supposed to be training medical scientists who will take things forward. So for all of those students who are hoping to shape the future of medicine, I think this is definitely a place where one should look. The problem generally speaking is that medical students, I think, have very good minds. They have retentive minds, but they tend to be somewhat less analytical than the students who go into physics and other pursuits like that.
So they are not at present well trained in some of the things that one needs to know in order to get over the hurdle of understanding ion channels. Part 2: Family Background and Leisure Pursuits Armstrong talks about his parents, his brother, his wife who is also a scientist , their four children and his interests in marathons and mountain climbing.
Where you grew up and your folks and brothers and sisters and stuff like that? And then both families, my maternal family, the Margraves, and the Armstrongs moved to Southeast Oklahoma. That was very interesting to hear about. But in any case, the Margraves, my grandfather and grandmother, had four daughters who were all lovely, interesting and intelligent. My father was the only surviving child of the Armstrongs, although my grandfather had 12 brothers, so that was a very large family.
My grandmother Armstrong died at a relatively young age, so they had only two children, one of whom did not survive. My father went off to join the Army during the First World War and never finished college. I was born in Chicago, where he was working in a bank until the Depression really hit strongly, and then we moved back to, first Oklahoma and then finally to Dallas, Texas, where he worked in the Federal Reserve Bank.
My maternal grandparents continued to live in Hugo, Oklahoma, and my paternal grandfather was a lawyer in a little town called Idabel, which was about 40 miles away. Well, it was an interesting place to visit, both of them—the cotton gins and so on. I have one brother and many, many cousins. It was always a very strong family because of the ties among the Margrave girls, who were really, really entertaining. My brother, in fact, lives in California, not too far from you.
He lives in San Jose, and is a very entertaining and intelligent person, always interesting to talk to on virtually any subject. Of the two of us, Bob was more interested in history and English literature, and I went into medicine.
I know your wife, Clara, is a distinguished scientist in her own right. Do you talk to her about the structure of the release apparatus in muscle fibers, and does she talk to you about how channels work? We talk to each other quite a bit. I learned a very great deal from Clara, including a positive attitude that, uh—I tend to be somewhat skeptical. Clara, on the other hand, is always enthusiastic about new work. And so her lessons to me in that regard have been very helpful, because I think in general that one learns much faster if you accept a new proposal and then have a very enthusiastic attitude toward it, and then later perhaps you can become more critical about it.
But the general initial acceptance I think is an important step in learning about it. John works for Compaq computer. Katie is married and living in Palo Alto, as a matter of fact, and she teaches school and her husband is there at Stanford--Will Talbot. Sandra plays the viola and is actually a professional, managing to make a living in what must be the hardest occupation of virtually any, because the competition is fierce. That is very impressive. That is wonderful. And I know that you like to run in your spare time.
I enjoy it part of the time. Running competitively is actually kind of fun, so I have even won a few races—in my age group. Have you done a marathon?
I have done six or eight marathons. I won my age group once upon a time in the Philadelphia marathon, so that was nice. You also do some mountain climbing with Clara I hear.
Clara has turned out to be a very good mountain climber, so we had a wonderful trip to Nepal this spring, as a matter of fact. And we were walking around at very high altitudes for, oh, three weeks, I guess, in a place called Inner Dolpo, which was extremely remote.
A very, very fascinating and trying trip. Both of us absolutely love that and would love to be back there even now. We had one preceding trip in which we went to the Everest region and got up quite close to the foot of Everest. Every corner has a new vista that is amazing to see. Part 3: Education and Training A graduate of Rice Institute in Dallas, Armstrong went to medical school at Washington University, where he first became interested in electrophysiology.
But could you tell me just a little bit about your educational odyssey? Well, life is a matter of chance. So I managed to get accepted to Rice Institute, which was certainly the best school, I would say still is the best school in Texas. I went there for my undergraduate degree, and I was very fond of the place—still am.
It was very rigorous in those days and not, I think, quite as accommodating to the students as it has become since. But the education there was absolutely first rate. The teachers, the professors were all in love with their subject. And they managed to communicate that very effectively. So, I took a course that was relatively heavy in science and then proceeded to Washington University, which is and was a most excellent medical school.
And I guess I had certain adjustments on leaving the ideal world of chemistry, physics, and coming to the much more empirical world involved in medicine. So anyway, that was an emotional shock. So certainly I had all of that feeling in trying to cope with medicine. But the first year, I was very fond of it. I liked biochemistry, even anatomy I liked a lot. But it was there in Washington University that I first got interested in electrophysiology. And George Bishop was one of their people colleagues.
Very strong minded, very intelligent, wonderful man, who was the electrophysiologist-in-residence of the Neurology Department at Washington University, and it was in his general environs that I was working as an electrophysiologist. In fact, I was in the screened room right next to his office and using equipment that he had designed for measuring brain waves. And that was quite a fascinating learning experience. I actually learned some things about the brain and the evoked potentials in the visual system that I think still would be worth investigating.
I was there working in the era, at roughly the same time as Hubel and Wiesel were doing their wonderful work on the connections of, well, basically the wiring of the visual system and the various types of receptive fields in areas 17, 18 and 19, and then the lateral geniculate.
Function and structure of ion channels
Similar authors to follow And I would suppose that very large numbers of those must modify the action of ion channels in one way or another. Inspired experiment and inference led hiple to propose that sodium channels become inactivated temporarily unable to open when a tethered ball attached to the channel becomes stuck in the open pore. And that turned out to be pretty hard. Their pores have the capacity to act as a molecular sieve.
Armstrong is a professor of physiology at the University of Pennsylvania in Philadelphia. Part 1: Ion Channels in Medicine and Biology "I think that ion channels are the most important single class of proteins that exist in the human body or any body for that matter," Dr. Armstrong tells a hypothetical skeptic from medical school. We can follow it more or less closely, depending on how it evolves. I wanted to ask you a little bit about how you see the place of ion channels in biology and medicine and then ask you a little bit about your family background and your family today.
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