Presynaptic actions of cholinergic agents upon the hair cell-afferent fiber synapse in the vestibular labyrinth of the frog.

Spontaneous activity of semicircular canal afferents in the isolated labyrinth of the frog is altered by bath application of cholinergic agonists. Muscarinic agonists can produce an increase in action potential frequency of individual afferents. This increase develops slowly and is prolonged in the time course of its action. Nicotinic agonists can either increase (most cases) or decrease afferent activity. These effects occur rapidly and decay during the period of activation, suggesting desensitization. Muscarinic effects are blocked by prior administration of atropine and nicotinic effects (both increases and decreases in action potential frequency) by curare. Intracellular recordings reveal that the nicotinic effects on afferent action potential frequency are the result of alterations in the frequency of spontaneous synaptic potentials, indicating a presynaptic site of action on the hair cells for these compounds. This conclusion is supported by the fact that in the presence of high Mg2+/low Ca2+, which blocks hair cell release of transmitter, cholinergic agonists do not affect the resting membrane potential of the vestibular afferent. Electrical stimulation of the VIIIth cranial nerve can result in either an increase or a decrease in spontaneous synaptic potential and action potential frequency of an afferent. These effects are blocked by prior administration of curare or of nicotinic agonists. Repetitive or continuous stimulation of the VIIIth nerve results in a reversible reduction of the evoked response, suggesting desensitization. Transection of the VIIIth cranial nerve two weeks prior to recording eliminates these actions of electrical stimulation, but not the responses to cholinergic agonists, indicating that the effects of electrical stimulation are mediated by centrally arising efferents. These findings confirm that acetylcholine is probably the transmitter released from centrally arising vestibular efferents, and, in addition, demonstrate that efferent-mediated effects are predominantly expressed through nicotinic receptors. Studies comparing the effects of isolation of the semicircular canal alone versus the intact labyrinth suggest that the method of isolation may be an important factor in determining whether efferent activity results in a predominant increase or decrease in afferent activity.