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default for PI page turquoise Dr Helen Kennedy
Signal transduction in the development of hearing

Full contact details
helen.kennedy@bristol.ac.uk
Department of Physiology and Pharmacology

Projects -  Diseases -  Processes -  Techniques -  Equipment -  Funding -  Collaborations -  Teaching -  Group members -  Publications & further information

Research

Auditory hair cells are responsible for our ability to hear, and irreversible damage of these delicate sensory cells is the most common cause of deafness in the UK.

My research focuses on the role of intracellular calcium in signal transduction in mammalian hair cells. Increases in intracellular calcium are involved in several important processes in mammalian hair cells and my lab focuses on its role in adaptation of the mechanotransducer current and in triggering of transmitter release.

The hair cell bundle is exquisitely sensitive to mechanical motion, with deflections of less than the diameter of an atom being sufficient to open transducer channels in vivo. We have studied the transducer current and its calcium dependent adaptation during development and after the onset of hearing. We have shown that the mammalian auditory system is capable of extremely fast adaptation in the order of 100 microseconds or less, and that the speed of adaptation is related to the characteristic frequency of the hair cell.

We are also interested in calcium signaling in the basal pole of the inner hair cell, close to afferent transmitter release sites. Using simultaneous patch-clamping and confocal imaging we have demonstrated that calcium induced calcium release occurs in the basal pole of hair cells. We are now studying its role in triggering transmitter release from the inner hair cell synapse during development of hearing.



Current projects include:
  • Calcium signalling in mammalian cochlear hair cells
  • The role of calcium induced calcium release in hair cell synaptic transmission
  • Mechanotransduction in outer hair cells

Possible future projects and direction of research:
  • Calcium signals and mechanotransduction in inner hair cells
  • The role of anion channels and co-transporters in outer hair cell function


Diseases related to this field of research
Hearing and balance deficit, deafness, develpomental and drug induced forms of deafness

Processes and functions relevant to this work
Hearing, development


Techniques in routine use
Whole-cell patch-clamp electrophysiology, capacitance measurements, confocal calcium imaging, RT-PCR


Equipment in routine use
Electrophysiological equipment, confocal microscope

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Projects -  Diseases -  Processes -  Techniques -  Equipment -  Funding -  Collaborations -  Teaching -  Group members -  Publications & further information

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Grants and funding

Wellcome Trust Project Grant 2005-2008

Collaborations

Prof. Robert Fettiplace, University of Madison Wisconsin USA

Teaching

Physiology III, Element Organiser: Auditory Neuroscience: Hearing and Deafness. Physiology II, Higher mental function.

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Members of the group

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Publications, recommended reading and further information

Kennedy, H.J., Crawford, A. C. and Fettiplace, R. (2005).
Force generation by mammalian hair bundles supports a role in cochlear amplification.
Nature 433, 880-883

Kennedy, H.J., Evans, M.J. and Fettiplace, R. (2003).
Fast adaptation of mechanoelectrical transducer channels in mammalian hair cells.
Nature Neuroscience 6(8), 832-836.

Kennedy, H.J. (2002).
Intracellular calcium regulation in inner hair cells from neonatal mice.
Cell Calcium. 31, 127-136.

Kennedy, H.J. and Meech, R.W. (2002).
Fast Ca 2+ signals at mouse inner hair cell synapse: a role for Ca 2+ induced Ca 2+release.
J. Physiol. 539, 15-23.

Gale, J.E., Marcotti, W., Kennedy, H.J., Kros, C.J. and Richardson, G.P. (2001)
FM-143 behaves as a permeant blocker of the Hair-cell’s mechanotransducer channel.
J. Neuroscience. 21(18), 7013-7025.

Please also find more information at http://www.bris.ac.uk/Depts/Physiology/new/pi/helen_kennedy/kennedy_intro.htm


Projects -  Diseases -  Processes -  Techniques -  Equipment -  Funding -  Collaborations -  Teaching -  Group members -  Publications & further information

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