Keynote Lecture

Prof. Dr. Philine Wangemann
Anatomy & Physiology Department
Kansas State University, Manhattan, Kansas, USA

Videomicroscopy of the developing inner ear: Contractions of the endolymphatic sac expand scala media of the cochlea

Normal growth and development of the inner ear requires dynamic control of the luminal fluid volumes in different compartments of the membranous labyrinth. Transepithelial fluid secretion and absorption are important mechanisms to control fluid volumes. Failures of fluid secretion due to mutations of KCNQ1, KCNE1 or SLC12A2 and failures of fluid absorption due to mutations of SLC26A4 or FOXI1 cause deafness. We raised the hypothesis that expandability and contractility are mechanisms in addition to secretion and absorption that provide dynamic control of luminal fluid volumes in the developing inner ear. Under this hypothesis we raised two questions: Is the endolymphatic sac of the developing membranous labyrinth ear contractile? Does contractility of the endolymphatic sac affect the fluid volume of scala media in the cochlea? To address these questions, we isolated inner ears from embryonic mice. In a first set of experiments, endolymphatic sacs were isolated, cannulated and perfused with a fluorescent dye. Fluid volumes were monitored by 4D confocal microscopy (LSM 880, Carl Zeiss). Endolymphatic sacs were found to be expandable when pressurized and contractile when superfused with P2X purinergic receptor agonists. Contractility was blocked by cytochalasin D suggesting dependence on actin polymerization. In a second set of experiments, intact inner ears were isolated, the luminal fluid volume was labelled with a fluorescent dye and volumes of the endolymphatic sac and the cochlear duct were simultaneously monitored. Contraction of the endolymphatic sac was found to cause expansion of scala media in the cochlea. These observations establish expandability and contractility of the endolymphatic sac as mechanisms of volume control in the developing inner ear.
Supported by NIH-R01-DC012151.