A ROLE FOR CHLORIDE IN THE SUPPRESSIVE EFFECT OF ACETYLCHOLINE ON AFFERENT VESTIBULAR ACTIVITY

Afferents of the frog semicircular canal (SCC) respond to acetylcholin e (ACh) application (0.3-1.0 mM) with a facilitation of their activity while frog saccular afferents respond with suppression (Guth et al., 1994). All recordings are of resting (i.e., non-stimulated) multiunit activity as previously reported (Guth et al., 1994). Substitution of 8 0% of external chloride (Cl-) by large, poorly permeant anions of diff erent structures (isethionate, methanesulfonate, methylsulfate, and gl uconate) reduced the suppressive effect of ACh in the frog saccular af ferents. This substitution did not affect the facilitatory response of SCC afferents to ACh. Chloride channel blockers were also used to tes t further whether Cl- is involved in the ACh suppressive effect. These included: niflumic and flufenamic acids, picrotoxin, 5-nitro-2-(-3-ph enylpropylamino)benzoic acid (NPPB), and 4,4'-dinitrostilbene-2,2'-dis ulfonic acid (DNDS). As with the Cl- substitutions, all of these agent s reduced the suppressive response to ACh in the saccule, but not the facilitatory response seen in the SCC. The suppressive effect of ACh o n saccular afferents is considered to be due to activation of a nicoti nic-like receptor (Guth et al., 1994; Guth and Norris, 1996). Taking i nto account the effects of both Cl- substitutions and Cl- channel bloc kers, we conclude that changes in Cl- availability influence the suppr essive effect of ACh and that therefore Cl- may be involved in this ef fect.