ADDITIONAL EVIDENCE AGAINST THE CHOLINERGIC NATURE OF EFFERENT FACILITATION IN THE ISOLATED FROG LABYRINTH

We have previously demonstrated that in the frog labyrinth the discharge of about half of the afferent fibres is reduced by the electrical activation of the efferent system, while that of the other units is increased. Evidence has been provided that inhibition is cholinergic in nature, whereas facilitation is not. On the other hand, ATP produces a transient facilitatory effect in all fibres which are under the facilitatory efferent control, while it does not affect the resting discharge of the inhibited units (Rossi et al., J. Physiol., 471, 17, 1994). A recent report has reproposed the thesis that a singie efferent system, releasing acetylcholine, exists in frog labyrinth; its activation would produce a decrease in the discharge of the afferent fibres which innervate one subpopulation of hair cells and an increase, through a different cholinergic receptor subtype, of the discharge in the other fibres (S. Cochran, Brain Res., 642, 334, 1994). The main evidence in favour of this idea is that the nlcotinic agonist dimethylphenylpiperazinium (DMPP) increases the resting discharge in some units while it decreases it in otbers; these effects are prevented by curare, which would block both inhibition and facilitation. To further investigate the possible cholinergic nature of facilitation. we recorded afferent mEPSP and spike rates from single fibres of the postericr nerve in the presence of d-tubocurarine (10-6, 10-5 M) or DMPP (2x10-5 M). Neither of them affected efferent facilitation; instead, both drugs increased the resting synaptic activity of all the units without modifying the fibre membrane potential thus suggesting that they were acting at a different, non cholinergic. site. Ca2+-dependent, voltage-independent K-channels of small conductance (SK) are present in the hair cell membrane. It is accepted that such channels are specifically blocked by curare or apamine. When apamine (10-7 M) was tested, an increase of the resting discharge similar to that produced by curare was observed, while facilitation was unaltered. Thus SK channels may be sensitive to both curare and DMPP, owing to the structural similarity of the two drugs. Blockade of K channels, which are open at normal resting potential, would depolarise the hair cell thereby increasing transmitter release at the cytoneural junction and the recorded mEPSP and spike activities in the afferent fibres. Cholinergic drugs may thus facilitate afferent transmitter release by acting on SK channels, rather than interfering with the efferent control of receptor discharge.