Effects of a calcium channel blocker on spontaneous neural noise and gross action potential waveforms in the guinea pig cochlea.
The effects of the L-type Ca2+ channel blocker nimodipine on the spectrum of the spontaneous neural noise (SNN) and the waveform of the gross sound-evoked compound action potential (CAP) were investigated by perilymphatic perfusion in the guinea pig cochlea. Both the SNN and the CAP were reversibly suppressed by nimodipine. The percentage reduction in SNN was dose-dependent in a manner very similar to the results obtained with the measures of CAP threshold changes. The reduction in the peak SNN caused by 10 microM nimodipine was the same as that caused by 500 microM kainic acid, which totally eliminated any neural responses. For 1 microM nimodipine there was an apparent dissociation between the SNN and CAP changes such that the SNN could be markedly suppressed with only very small changes in CAP thresholds. These results imply that spontaneous release of neurotransmitter from the inner hair cell is more sensitive to block of calcium channels than evoked release. There was no evidence for any marked shift caused by nimodipine, in the position of the main (900 Hz) spectral peak in the SNN. Comparison of the CAP waveform before and after nimodipine perfusion showed that the CAP waveforms were unchanged despite the change in sensitivity. These data do not support the notion of any significant postsynaptic site of action of nimodipine. The data hence provide further support for an exclusively presynaptic role for L-type Ca2+ channels in the regulation of both evoked and spontaneous neurotransmitter release from inner hair cells.
Sueta
T
T
Department of Otolaryngology, Fukuoka University, Fukuoka, Japan.
Zhang
S Y
SY
Sellick
P M
PM
Patuzzi
R
R
Robertson
D
D
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000502:physiology; D003051:Cochlea / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D005260:Female; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D009553:Nimodipine / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018377:Neurotransmitter Agents; D009553:Nimodipine