Caffeine and ryanodine demonstrate a role for the ryanodine receptor in the organ of Corti

The hypothesis that the release of Ca2+ from ryanodine receptor activated Ca2+ stores in vivo can affect the function of the cochlea was tested by examining the effects of caffeine (1-10 mM) and ryanodine (1-333 muM), two drugs that release Ca2+ from these intracellular stores. The drugs were infused into the perilymph compartment of the guinea pig cochlea while sound (10 kHz) evoked cochlear potentials and distortion product otoacoustic emissions (DPOAEs; 2f(1)-f(2) = 8 kHz, f(2) = 12 kHz) were monitored. Caffeine significantly suppressed the compound action potential of the auditory nerve (CAP) at low intensity (56 dB SPL; 3.3 and 10 mM) and high intensity (92 dB SPL; 10 mM), increased N1 latency at high and low intensity (3 and 10 mM) and suppressed low intensity summating potential (SP; 10 mM) without an effect on high intensity SP. Ryanodine significantly suppressed the CAP at low intensity (100 and 333 M) and at high intensity (333 muM), increased NI latency at low intensity (33, 100 and 333 muM) and at high intensity (333 muM) and suppressed low intensity SP (100 and 333 muM) and increased high intensity SP (333 PM). The cochlear microphonic (CM) evoked by 10 kHz tone bursts was not affected by caffeine at high or low intensity, and ryanodine had no effect on it at low intensity but decreased it at high intensity (10, 33, 100 and 333 muM). In contrast, caffeine (10 mM) and ryanodine (33 and 100 muM) significantly increased CM evoked by 1 kHz tone bursts and recorded from the round window. Caffeine (10 mM) and ryanodine (100 M) reversibly suppressed the cubic DPOAEs evoked by low intensity primaries. Overall, low intensity evoked responses were more sensitive and were suppressed to a greater extent by both drugs. This is consistent with the hypothesis that release of Ca2+ from ryanodine receptor Ca2+ stores, possibly in outer hair cells and supporting cells, affects the function of the cochlear amplifier. (C) 2002 Elsevier Science B.V. All rights reserved.