TY - JOUR

T1 - Hydrogen peroxide inhibits gap junctional coupling and modulates intracellular free calcium in cochlear Hensen cells

AU - Todt, I

AU - Ngezahayo, A

AU - Ernst, A

AU - Kolb, H A

PY - 2001/5/15

Y1 - 2001/5/15

N2 - The double whole-cell patch-clamp configuration was applied to analyze gap junctional conductance (Gj) of isolated pairs of cochlear supporting Hensen cells of guinea pig under control conditions and in the presence of hydrogen peroxide (H2O2). Under control conditions, the dependence of Gj on transjunctional voltage (Vj) appeared to vary between different cell pairs with a maximum value of about 40 nS at Vj close to 0 mV. The voltage dependence and the maximum amplitude of Gj stayed constant for at least 2 hr. Addition of H2O2 to the bath at concentrations above 0.08 mm caused a significant decrease of Gj, but the membrane potential of about -30 mV was not affected. 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, while 0.08 mm H2O2 evoked an oscillating-like behavior of [Ca2+]i. We propose that the H2O2-evoked inhibition of gap junctional coupling of Hensen cells is closely related to pathophysiological conditions such as noise- induced hearing loss, aminoglycoside-related ototoxicity and presbycusis, which are known to be associated with production of free radicals.

AB - The double whole-cell patch-clamp configuration was applied to analyze gap junctional conductance (Gj) of isolated pairs of cochlear supporting Hensen cells of guinea pig under control conditions and in the presence of hydrogen peroxide (H2O2). Under control conditions, the dependence of Gj on transjunctional voltage (Vj) appeared to vary between different cell pairs with a maximum value of about 40 nS at Vj close to 0 mV. The voltage dependence and the maximum amplitude of Gj stayed constant for at least 2 hr. Addition of H2O2 to the bath at concentrations above 0.08 mm caused a significant decrease of Gj, but the membrane potential of about -30 mV was not affected. 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, while 0.08 mm H2O2 evoked an oscillating-like behavior of [Ca2+]i. We propose that the H2O2-evoked inhibition of gap junctional coupling of Hensen cells is closely related to pathophysiological conditions such as noise- induced hearing loss, aminoglycoside-related ototoxicity and presbycusis, which are known to be associated with production of free radicals.

KW - Animals

KW - Calcium/metabolism

KW - Calcium Signaling/drug effects

KW - Cochlea/cytology

KW - Electric Conductivity

KW - Gap Junctions/drug effects

KW - Guinea Pigs

KW - Hydrogen Peroxide/pharmacology

KW - Intracellular Fluid/drug effects

KW - Patch-Clamp Techniques

U2 - 10.1007/s00232001-0014-4

DO - 10.1007/s00232001-0014-4

M3 - Article

C2 - 11420597

VL - 181

SP - 107

EP - 114

JO - The journal of membrane biology

JF - The journal of membrane biology

SN - 0022-2631

IS - 2

ER -