The mechanism and site of action of lidocaine hydrochloride in guinea pig inner ear.
Lidocaine was applied to the round window (RW) in order to localize its site of action in the cochlea. Cochlear microphonic (CM), summating potential (SP), and compound action potential (CAP) input/output functions were measured to a 16 kHz tone burst to assess the functional changes of the cochlea. In separate experiments, the effect of lidocaine on the whole cell current of isolated outer hair cells (OHC) was studied. A dose of 2 microliters of 40 mM lidocaine in saline solution, when applied to the RW, caused a small change in all measured variables, indicating a passage of the drug through the RW membrane to sites of action. However, 160 mM of lidocaine further decreased CM, SP, and CAP by a total of 40% from the control. A partial recovery occurred for CM during the 30 min follow-up period. CAP and SP continued to decline. In isolated OHCs, lidocaine decreased the whole cell current in a dose-dependent fashion. The KD for lidocaine effect on OHCs was 7 mM. Our in vivo results indicate that lidocaine affects OHCs and reduces CM, causing a subsequent reduction in SP and CAP. The increased effect of lidocaine on CAP and SP, while CM is recovering, suggests an additional specific effect of lidocaine on the cochlear nerve and/or on inner hair cells. Considering that lidocaine alters OHC current (in isolated hair cells) and that lidocaine does not affect endocochlear potential [Laurikainen et al. Acta Otolaryngol (Stockh) 1991: 112: 800-9], the observed CM changes are most likely due to an in vivo effect on OHCs. Thus, the early effect of lidocaine on the cochlea appears to be due to a significant change in organ of Corti function, rather than to direct anesthesia of the cochlear nerve. Later, an independent effect of the drug may occur on neural tissues in the inner ear.
Laurikainen
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Department of Otolaryngology, Turku University Central Hospital, Finland. eslaur@utu.fi
Lin
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Nuttall
A L
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Dolan
D F
DF
D000818:Animals; D003051:Cochlea / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism*; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism*; D008012:Lidocaine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D009925:Organ of Corti / Q000378:metabolism*
D008012:Lidocaine