Cell membrane lipids affect the mechano-electrical transduction channel. PIP2 (phosphatidylinositol-4,5-bisphosphat) specifically modulating single channel conductance and ion selectivity

Introduction:

Hearing utilizes sensory cells, hair cells, to translate mechanical stimuli into electro/chemical signals, termed mechano-electrical transduction (MET). MET occurs in the sensory organelle of hair cells, the hair bundle. An auditory hair bundle consists of three rows of stereocilia that are arranged in a staircase pattern. Positive deflections open MET channels, depolarizing the cell, resulting in a graduated neurotransmitter release. Hair bundle deflection could gate the MET channel via a chain of protein/protein interactions or via a force relay through the cell membrane.

Methods:

We utilized whole-cell patch clamping, Ca2+ imaging, and immunohistochemial techniques to investigate MET currents of hair cells. We used several drugs to block PIP₂ enzymatic replenishment, which lead to a drop of PIP₂ levels below the detection limit after ca. 10 – 15 minutes.

Results:

We show that PIP₂ localizes close to the presumed MET-channel location and PIP₂ manipulations affect MET-channel properties, including a reduction of peak MET-currents and adaptation, an increase of resting open probability, as well as a change in single channel conductance, ion selectivity, and Ca²⁺ dependent MET-current block. These properties are usually attributed to proteins of the MET machinery.

Conclusions:

Our data shows that PIP₂ is important for the normal function of the mammalian MET-channel and its loss effects single channel properties. Beyond PIP₂ we also find effects of other lipid species and cholesterol on MET-channel function, pointing out possible explanations for previous findings of a correlation between sudden sensorineural hearing loss and the lipid profile of those patients.

Publication History

Publication Date:
23 April 2019 (online)