In the frog vestibular organs, about 50% of the sensory units are inhibited by a cholinergic efferent system, whereas the others are potentiated by a separate purinergic mechanism (Rossi et al., Brain Res., 185, 125, 1980; Brain Res., 555, 123, 1991; J. Physiol., 478, 17, 1994). Recently, S. Cochran (Brain Res., 642, 334, 1994) claimed that in the frog labyrinth a single efferent system decreases or increases the discharge of each individual unit by acting through two different cholinergic receptor subtypes. The main evidence was that both the activating and depressing actions of the nicotinic agonist DMPP are prevented by curare, which would block both inhibition and facilitation. To further investigate the possible cholinergic nature of facilitation, we recorded mEPSP and spike rates from single fibres of the posterior nerve in the presence of d-tubocurarine (10-6 -10-5M) or DMPP (2x10-5 M). Neither drug affected efferent facilitation. Instead, both drugs increased synaptic activity in all units; this suggests a non-cholinergic site of action. The maximal effects of the two drugs were not additive, thereby pointing to a common mechanism. Ca2+-dependent, voltage-independent potassium channels of small conductance (SK) are present in the hair cell membrane. It is well accepted that such channels are specifically blocked by curare or apamine. Apamine (10-7 M) produced an increase in the discharge similar to curare, with no effect on facilitation. We suggest that 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 both mEPSP and spike activities in the afferent fibres. Facilitation by curare and DMPP may thus occur independent of cholinergic receptors and efferent control. Curare would therefore interfere with inhibition by blocking cholinergic receptors and simultaneously occlude DMPP facilitatory effects through SK channel block.
The effects of dimethylphenylpiperazinium (DMPP), curare and apamine on the sensory discharge and its efferent control in the frog labyrinth
ROSSI, Marialisa;MARTINI, Marta;PELUCCHI, Bruna;RUBBINI, Gemma;
1997
Abstract
In the frog vestibular organs, about 50% of the sensory units are inhibited by a cholinergic efferent system, whereas the others are potentiated by a separate purinergic mechanism (Rossi et al., Brain Res., 185, 125, 1980; Brain Res., 555, 123, 1991; J. Physiol., 478, 17, 1994). Recently, S. Cochran (Brain Res., 642, 334, 1994) claimed that in the frog labyrinth a single efferent system decreases or increases the discharge of each individual unit by acting through two different cholinergic receptor subtypes. The main evidence was that both the activating and depressing actions of the nicotinic agonist DMPP are prevented by curare, which would block both inhibition and facilitation. To further investigate the possible cholinergic nature of facilitation, we recorded mEPSP and spike rates from single fibres of the posterior nerve in the presence of d-tubocurarine (10-6 -10-5M) or DMPP (2x10-5 M). Neither drug affected efferent facilitation. Instead, both drugs increased synaptic activity in all units; this suggests a non-cholinergic site of action. The maximal effects of the two drugs were not additive, thereby pointing to a common mechanism. Ca2+-dependent, voltage-independent potassium channels of small conductance (SK) are present in the hair cell membrane. It is well accepted that such channels are specifically blocked by curare or apamine. Apamine (10-7 M) produced an increase in the discharge similar to curare, with no effect on facilitation. We suggest that 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 both mEPSP and spike activities in the afferent fibres. Facilitation by curare and DMPP may thus occur independent of cholinergic receptors and efferent control. Curare would therefore interfere with inhibition by blocking cholinergic receptors and simultaneously occlude DMPP facilitatory effects through SK channel block.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
