Toluene can perturb the neuronal voltage-dependent Ca2+ channels involved in the middle-ear reflex

Numerous laboratory-based data have shown the ability of toluene (Tol) to exacerbate noise-induced hearing loss. However, the mechanism responsible for the synergistic effects of a coexposure to noise and Tol has not yet been completely elucidated. Recent investigations in rats have focused on quantifying the anticholinergic effects of certain aromatic solvents and have demonstrated that these solvents can cancel the protective role played by the middle-ear reflex (MER). Voltage-dependent Ca(2+) channels (VDCCs) regulate acetylcholine release in the central synaptic network and control muscular excitation/contraction processes as well. In order to identify the prevailing action of Tol in the central or peripheral compartment of the MER arc, two VDCC antagonists were injected into the common carotid trunk: omega-conotoxin MVIIC, which blocks only the neuronal N- and P/Q-type Ca(2+) channels, or verapamil, which inhibits the muscular L-type Ca(2+) channels. Rats were also implanted with an electrode on the round window membrane to measure the cochlear microphonic potential (CMP) elicited with a band noise centered at 4 kHz and emitted at 85 dB sound pressure level. The variations in CMP recorded during the test compound injection showed that Tol has similar effects to those induced by omega-conotoxin, the neuronal VDCC blocker. The response obtained with the verapamil injection was broader than those obtained with Tol or conotoxin. This investigation therefore revealed that Tol can mimic the effects of VDCC blockers. The antagonist effects of Tol would be closer to neuronal than to muscular blockers and would be presumably located at the level of the integrator centers of the reflex.