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Hudspeth proposed the existence of a "gating spring" opened by direct mechanical force that would open a hypothetical channel responsible for the entry of calcium ions. The hypothesis was based on the following evidence: 1) Part of the energy needed to bend the filament bundle was mysteriously lost, but could be explained if it was used to opening this gating spring, 2) The entry of calcium ions was microseconds long, this is so fast that only direct opening -without a cascade of chemical reactions- could account for it and 3) Hudspeth tested a model analogue to the opening of a door with a string attached to the door knob and demonstrated that a similar process was taking place when the filaments of the hair cell moved. Furthermore, microscopic evidence showed the existence of such a string-like structure tethering the tip of one filament to the side of and adjacent filament that could be the elusive gating spring; this string—called the tip link—would tense if the filament bundle was bent and then open the channel. Although the precise identity of the proteins forming the tip link and the mechanosensitive channel is still controversial 30 years later. Hudspeth's hypothesis was correct and fundamental for the understanding of the sense of
42:
230:, the sensory cells of the cochlea. Hudspeth's bold interpretation of the data obtained in his careful experimental research combined with biophysical modelling lead him to propose for the first time that the sense of hearing depends on a channel that is opened by mechanical force: The hair cells located in the
1067:"A combination of high-resolution experiments and detailed numerical modelling of fluid-structure interactions reveals the physical principles behind the basic structural features of hair bundles and shows quantitatively how these organelles are adapted to the needs of sensitive mechanotransduction"
743:
Holton, T.; Hudspeth, A. J. (1983). "In this study from 1983, quantitative measurements were made of the motion of individual hair bundles in an excised preparation of the cochlea stimulated at auditory frequencies. The angular displacement of hair bundles is frequency selective and tonotopically
238:
when their apical end -consisting of a bundle of filaments- bends in response to the movement caused by this sound. The activated hair cell rapidly fills with calcium entering from the outside of the cell, which in turn activates the release of neurotransmitters that start a signal to the brain.
546:"Corey, D.P., Hudspeth, A.J. (1983) Kinetics of the receptor current in bullfrog saccular hair cells J Neuro 3 (5): 962–976 : In this paper, the direct mechanical opening necessary for the sense of hearing is stated for the first time"
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in 1968. He enrolled in a graduate program in neurobiology to avoid being drafted into the military, but a year later the policy was changed, requiring him to enter medical school for exemption. He studied under Nobel prize winners
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643:"Bartsch TF & Hudspeth AJ. et al (2019) Elasticity of individual protocadherin 15 molecules implicates tip links as the gating springs for hearing. Proc Natl Acad Sci U S A. 28; 116(22):11048-11056"
969:"These results suggest that the Ca2+ current drives the cochlear active process, and they support the hypothesis that active hair-bundle motility underlies cochlear amplification"
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Bartsch, T. F.; Hengel, F. E.; Oswald, A.; Dionne, G.; Chipendo, I. V.; Mangat, S. S.; El
Shatanofy, M.; Shapiro, L.; Müller, U.; Hudspeth, A. J. (2019).
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2002 Award of Merit, Association for
Research in OtolaryngologyForces between clustered stereocilia minimize friction in the ear on a subnanometre scale.
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830:"Revisiting how a molecular gradient of a potassium channel allows the chicken cochlea to sense progressively lower tones along its structure"
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in New York City, where he is director of the F.M. Kirby Center for
Sensory Neuroscience. His laboratory studies the physiological basis of
1209:
694:"Qiu, X., & Müller, U. (2018). Mechanically Gated Ion Channels in Mammalian Hair Cells. Frontiers in cellular neuroscience, 12, 100"
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Neuron (1997): 19(5): 1061–1075 (note: this research was continued several years later taking advantage of newly available technology)
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928:"This research shows the embryonic development of the har cells necessary for the zebrafish directional movement in the water"
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879:"In this review AJ Hudspeth explains the biophysics of the hearing in the light of his own vast contribution to the field"
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Directional cell migration establishes the axes of planar polarity in the posterior lateral-line organ of the zebrafish.
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AS, Baumgart J, Risler T, Versteegh CP, A.J. Hudspeth. Nature. 2011 May 22;474(7351):376-9. doi: 10.1038/nature10073.
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Hudspeth, A. J.; Versteegh, Corstiaen P. C.; Risler, Thomas; Baumgart, Johannes; Kozlov, Andrei S. (June 2011).
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istribution of Ca2+-activated K+ channel isoforms along the tonotopic gradient of the chicken's cochlea.
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As a teenager, James
Hudspeth spent his summers working as a technician in the lab of neurophysiologist
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781:"This landmark research has been featured in the textbook "Molecular Cell Biology" by JE Darnell"
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1116:"The spatial pattern of cochlear amplification note: featured as a cover of this journal issue"
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Hudspeth, A. J. (1989). "AJ Hudspeth (1989) How the ear's works work Nature 341 page 397-404".
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Coherent motion of stereocilia assures the concerted gating of hair-cell transduction channels.
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148:. Hudspeth was expelled from high school for mixing dangerous chemicals and other mischief.
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Forces between clustered stereocilia minimize friction in the ear on a subnanometre scale.
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from 1989 until 1995, when the department was closed. In 1995, he was recruited to the
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López-Schier, H.; Starr, C. J.; Kappler, J. A.; Kollmar, R.; Hudspeth, A. J. (2004).
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where he was a professor from 1983 to 1989. He directed the neuroscience program at
168:. He completed both programs and received his PhD in 1973 and MD in 1974, both from
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1018:"Research showing the coordinated movement of the entire hair cell filament bundle"
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Fisher, J. A.; Nin, F.; Reichenbach, T.; Uthaiah, R. C.; Hudspeth, A. J. (2012).
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organized, demonstrating the existence of a micromechanical tuning mechanism".
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Proceedings of the
National Academy of Sciences of the United States of America
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Ca2+ current-driven nonlinear amplification by the mammalian cochlea in vitro
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Micromechanical contribution to cochlear tuning and tonotopic organization.
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he spatial pattern of cochlear amplification Neuron (2012): 76(5):989–9
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Rosenblatt, K. P.; Sun, Z. P.; Heller, S.; Hudspeth, A. J. (1997).
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Kinetics of the receptor current in bullfrog saccular hair cells.
191:
Following his postdoctoral training, Hudspeth was a professor at
211:
1198:
307:
Kozlov AS, Baumgart J, Risler T, Versteegh CP, A.J. Hudspeth
828:
Miranda-Rottmann, S.; Kozlov, A. S.; Hudspeth, A. J. (2010).
477:"The Rockefeller University » Scientists & Research"
314:
Fisher JA, Nin F, Reichenbach T, Uthaiah RC, A.J. Hudspeth T
1640:
Members of the United States
National Academy of Sciences
175:
He began a postdoctoral fellowship with Åke Flock at the
286:
H, Starr CJ, Kappler JA, Kollmar R, A.J. Hudspeth
269:
Rosenblatt KP, Sun ZP, Heller S, A.J. Hudspeth D
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1016:Kozlov, A. S.; Risler, T.; Hudspeth, A. J. (2007).
84:
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201:University of Texas Southwestern Medical Center
155:in 1967, and received his master's degree from
1210:
513:"James Hudspeth, MD, PhD | Duke Neurobiology"
8:
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1645:California Institute of Technology faculty
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544:Hudspeth, A. J.; Corey, D. P. (May 1983).
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358:2010 Guyot Prize, University of Groningen
333:1991 K.S. Cole Award, Biophysical Society
300:Kozlov AS, Risler T, A.J. Hudspeth
297:. Nature Neuro (2005): 8(2):149–155
195:from 1975 to 1983. He then moved to the
495:"A. James Hudspeth, MD, PhD | HHMI.org"
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1650:Kavli Prize laureates in Neuroscience
967:Chan, D. K.; Hudspeth, A. J. (2005).
367:American Academy of Arts and Sciences
7:
593:
591:
539:
537:
459:"A. James Hudspeth – Our Scientists"
290: Dev CELL (2004): 7(3):401–412
259:Science (1983); 222 (4623): 508–510
698:Frontiers in Cellular Neuroscience
563:10.1523/JNEUROSCI.03-05-00962.1983
222:Hudspeth's research is focused on
179:, but returned soon afterwards to
25:
877:Hudspeth, A. J. (November 1997).
311:Nature. (2011): 474 (7351):376–9
304:Nature Neuro (2007): 10(1):87–92
27:American neutroscience professor
1187:Louisa Gross Horwitz Prize 2020
266:J. Neurosci., 3 (1983): 962-976
226:, and the deterioration of the
124:is the F.M. Kirby Professor at
1635:Rockefeller University faculty
834:Molecular and Cellular Biology
373:American Philosophical Society
293:Chan DK, A.J. Hudspeth
252:Holton T & A.J. Hudspeth
1:
1630:Harvard Medical School alumni
896:10.1016/S0896-6273(00)80385-2
798:10.1016/S0896-6273(00)80397-9
381:in Neuroscience (shared with
280:NEURON (1997): 19(5): 947-950
1323:Jørgen Christensen-Dalsgaard
1132:10.1016/j.neuron.2012.09.031
945:10.1016/j.devcel.2004.07.018
692:Qiu, X.; Müller, U. (2018).
363:National Academy of Sciences
352:2003 Ralph W. Gerard Prize,
371:2015 Elected member of the
262:D.P. Corey, A.J. Hudspeth
1666:
394:Louisa Gross Horwitz Prize
336:1994 Charles A. Dana Award
224:sensorineural hearing loss
146:Baylor College of Medicine
214:investigator since 1993.
115:
77:
39:
711:10.3389/fncel.2018.00100
354:Society for Neuroscience
151:Hudspeth graduated from
136:Early life and education
758:10.1126/science.6623089
660:10.1073/pnas.1902163116
550:Journal of Neuroscience
197:UCSF School of Medicine
1462:Armand Paul Alivisatos
1408:Emmanuelle Charpentier
361:Elected member of the
329:W. Alden Spencer Award
205:Rockefeller University
181:Harvard Medical School
126:Rockefeller University
107:Rockefeller University
73:in Neuroscience (2018)
210:Hudspeth has been an
1585:Christopher A. Walsh
1452:George M. Whitesides
1168:search.amphilsoc.org
1164:"APS Member History"
846:10.1128/MCB.00073-10
481:www2.rockefeller.edu
278:How hearing happens.
177:Karolinska Institute
1374:Mildred Dresselhaus
1083:10.1038/nature10073
1022:Nature Neuroscience
973:Nature Neuroscience
653:(22): 11048–11056.
1416:Virginijus Šikšnys
1307:Ewine van Dishoeck
1287:Alexei Starobinsky
1245:Donald Lynden-Bell
932:Developmental Cell
517:www.neuro.duke.edu
434:"The Ears Have It"
247:Noted publications
170:Harvard University
157:Harvard University
56:Harvard University
1612:
1611:
1577:Jean-Louis Mandel
1571:Ardem Patapoutian
1557:Robert Fettiplace
1553:A. James Hudspeth
1543:Michael Merzenich
1511:Cornelia Bargmann
1426:Maximilian Haider
1337:David Charbonneau
1255:Raymond N. Wilson
1077:(7351): 376–379.
606:(6241): 397–404.
402:Robert Fettiplace
387:Robert Fettiplace
122:A. James Hudspeth
119:
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79:Scientific career
34:A. James Hudspeth
16:(Redirected from
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1599:Winrich Freiwald
1501:Thomas C. Südhof
1497:Richard Scheller
1458:Robert S. Langer
1398:Christoph Gerber
1273:Michael E. Brown
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