Hydrogen peroxide inhibits gap junctional coupling and modulates intracellular free calcium in cochlear Hensen cells

The double whole-cell patch-clamp configuration was applied to analyze gap junctional conductance (G(j)) of isolated pairs of cochlear supporting Hens en cells of guinea pig under control conditions and in the presence of hydr ogen peroxide (H2O2). Under control conditions, the dependence of Gj on tra nsjunctional voltage (V,) appeared to vary between different cell pairs wit h a maximum value of about 40 nS at V-j close to 0 mV. The voltage dependen ce and the maximum amplitude of G(j) stayed constant for at least 2 hr. Add ition of H2O2 to the bath at concentrations above 0.08 mM caused a signific ant decrease of C, but the membrane potential of about -30 mV was not affec ted. In parallel, intracellular free calcium ([Ca2+](i)) was followed using fura-2. At 0.8 mM H2O2, a sustained increase of [Ca2+](i) was observed, wh ile 0.08 mM H2O2 evoked an oscillating-like behavior of [Ca2+](i). We propo se that the H2O2-evoked inhibition of gap junctional coupling of Hensen cel ls is closely related to pathophysiological conditions such as noise-induce d hearing loss, aminoglycoside-related ototoxicity and presbycusis, which a re known to be associated with production of free radicals.