Quantifying the Role of Ca2+ in Mechanotransduction

Louisiana State Univ Hsc New Orleans, New Orleans LA

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Abstract

DESCRIPTION (provided by applicant): Mechanoelectric transduction (MET) in auditory hair cells employs multiple Ca2+ dependent processes that regulate activation, adaptation and the steady-state properties of the channel. These processes may be mediated either directly at the MET channel, as with Ca2+ block of the pore, or indirectly through accessory structures, such as myosin and its regulation of slow adaptation. Separately quantifying these processes is complicated by the fact that most are not only sensitive to both mechanical perturbation and Ca2+ but also exhibit interdependence: changes in the properties of one process elicit changes in another. For example, because adaptation is sensitive to stimulus rise time, alterations in activation kinetics are predicted to change adaptation. Thus, devising means to alter these processes independently is needed to better quantify their role in MET. The experiments are designed to circumvent these issues by using flash photolysis to regulate intracellular Ca2+ independently from mechanical stimulation. Understanding how Ca2+ regulates activation and adaptation has taken on more significance, as tonotopic variance in these processes suggests their kinetics are important in establishing a bandpass filter that may play a role in the tuning required for outer hair cell motility and the active process.