Eckrich, Tobias (2012) Voltage gated Na+ channels and spontaneous action potential activity in cochlear hair cells during development. PhD thesis, University of Sheffield.
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Inner hair cells (IHCs) are the true sensory cells for sound. They receive acoustic stimuli and transduce them into graded receptor potentials that lead to the excitation of afferent nerve fibres, which transmit the sound information to the brain where the impression of sound arises. Before hearing onset IHCs transiently generate spontaneous calcium action potentials without the input of sound (Marcotti et al., 2003a). This activity is thought to orchestrate important developmental processes such as the refinement of synaptic connections and/or intrinsic IHC development such as that of ion channels and synaptic proteins (Kros et al., 1998). Various membrane currents influence IHC action potentials, including a transiently expressed tetrodotoxin sensitive sodium current (Marcotti et al., 2003b). In this thesis, electrophysiological recordings from rat IHCs were performed as a function of postnatal development and cochlear region in order to characterise the frequency and pattern of the spontaneous activity as well as the biophysical properties of the sodium current. By using in situ hybridisation it was attempted to reveal the molecular identity of the Na+ channel subunits expressed in immature IHCs. Electrophysiological recordings revealed that rat IHCs spontaneously generate action potentials until the end of the first postnatal week. Thereafter, action potentials could still be triggered using depolarising current injections until just before the onset of hearing. A rapidly activating and inactivating sodium current was observed in all immature IHCs investigated. This sodium current showed high temperature dependence and both its size and kinetics changed as a function of development and IHC position along the cochlea. Altogether, these results deepen our knowledge about the characteristics of the spontaneous action potential activity and reveal that the sodium current is active at physiological cell membrane potentials and involved in action potential generation.
|Item Type:||Thesis (PhD)|
|Academic Units:||The University of Sheffield > Faculty of Science (Sheffield) > Biomedical Science (Sheffield)
The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Biomedical Science (Sheffield)
|Depositing User:||Mr Tobias Eckrich|
|Date Deposited:||08 Oct 2012 14:23|
|Last Modified:||08 Aug 2013 08:49|