Journal
JOURNAL OF NEUROSCIENCE
Volume 37, Issue 48, Pages 11632-11646Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1351-17.2017
Keywords
adaptation; cell membrane; hair cell; mechanotransduction; PIP2
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Funding
- German Research Foundation [Deutsche Forschungsgemeinschaft] [EF100/1]
- National Institute on Deafness and Other Communication Disorders (NIDCD) [R00 DC013299]
- NIDCD [R01 DC003896, P30-044992]
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Membrane proteins, such as ion channels, interact dynamically with their lipid environment. Phosphoinositol-4,5-bisphosphate (PIP2) can directly or indirectly modify ion-channel properties. In auditory sensory hair cells of rats (Sprague Dawley) of either sex, PIP2 localizes within stereocilia, near stereocilia tips. Modulating the amount of free PIP2 in inner hair-cell stereocilia resulted in the following: (1) the loss of a fast component of mechanoelectric-transduction current adaptation, (2) an increase in the number of channels open at the hair bundle's resting position, (3) a reduction of single-channel conductance, (4) a change in ion selectivity, and (5) a reduction in calcium pore blocking effects. These changes occur without altering hair-bundle compliance or the number of functional stereocilia within a given hair bundle. Although the specific molecular mechanism for PIP2 action remains to be uncovered, data support a hypothesis for PIP2 directly regulating channel conformation to alter calcium permeation and single-channel conductance.
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