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Dopaminergic modulation of the voltage-gated sodium current in the cochlear afferent neurons of the rat.

Valdés-Baizabal C, Soto E, Vega R - PLoS ONE (2015)

Bottom Line: Recordings of the INa showed that DA receptor activation induced a significant inhibition of the peak current amplitude, leading to a significant decrease in cell excitability.The action of the D1- and D2-like receptors was shown to be mediated by a Gαs/AC/cAMP/PKA and Gαq/PLC/PKC pathways respectively.These results showed that DA receptor activation constitutes a significant modulatory input to SGNs, effectively modulating their excitability and information flow in the auditory pathway.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México.

ABSTRACT
The cochlear inner hair cells synapse onto type I afferent terminal dendrites, constituting the main afferent pathway for auditory information flow. This pathway receives central control input from the lateral olivocochlear efferent neurons that release various neurotransmitters, among which dopamine (DA) plays a salient role. DA receptors activation exert a protective role in the over activation of the afferent glutamatergic synapses, which occurs when an animal is exposed to intense sound stimuli or during hypoxic events. However, the mechanism of action of DA at the cellular level is still not completely understood. In this work, we studied the actions of DA and its receptor agonists and antagonists on the voltage-gated sodium current (INa) in isolated cochlear afferent neurons of the rat to define the mechanisms of dopaminergic control of the afferent input in the cochlear pathway. Experiments were performed using the voltage and current clamp techniques in the whole-cell configuration in primary cultures of cochlear spiral ganglion neurons (SGNs). Recordings of the INa showed that DA receptor activation induced a significant inhibition of the peak current amplitude, leading to a significant decrease in cell excitability. Inhibition of the INa was produced by a phosphorylation of the sodium channels as shown by the use of phosphatase inhibitor that produced an inhibition analogous to that caused by DA receptor activation. Use of specific agonists and antagonists showed that inhibitory action of DA was mediated both by activation of D1- and D2-like DA receptors. The action of the D1- and D2-like receptors was shown to be mediated by a Gαs/AC/cAMP/PKA and Gαq/PLC/PKC pathways respectively. These results showed that DA receptor activation constitutes a significant modulatory input to SGNs, effectively modulating their excitability and information flow in the auditory pathway.

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Effects of TTX, nickel and nifedipine on the INa.A) INa produced by voltage pulses from −110 mV to 50 mV in control conditions, during 100 nM TTX perfusion and 2 min after washout. In this and the following figures, only representative traces are shown. B) Current-voltage relationship in control conditions (black) and with TTX perfusion (blue). C) Current recording in control conditions and after coapplication of 10 μM nifedipine (Nfd) and 100 μM nickel. D) Current-voltage relationship in control conditions (black) and with Ni2+ plus nifedipine perfusion (red). In all traces, the dotted line indicates zero current.
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pone.0120808.g001: Effects of TTX, nickel and nifedipine on the INa.A) INa produced by voltage pulses from −110 mV to 50 mV in control conditions, during 100 nM TTX perfusion and 2 min after washout. In this and the following figures, only representative traces are shown. B) Current-voltage relationship in control conditions (black) and with TTX perfusion (blue). C) Current recording in control conditions and after coapplication of 10 μM nifedipine (Nfd) and 100 μM nickel. D) Current-voltage relationship in control conditions (black) and with Ni2+ plus nifedipine perfusion (red). In all traces, the dotted line indicates zero current.

Mentions: The average capacitance of SGNs (n = 380) was 9 ± 0.5 pF. Some cells were identified as basal or apical cells, and no difference in membrane capacitance was found between cells from basal (8 ± 0.4 pF, n = 52) or apical portion of the cochlea (8 ± 0.3 pF, n = 85). The INa was blocked by TTX (Fig. 1A-B) and unaltered by the calcium channel antagonists nifedipine (10 μM) and nickel (100 μM) (Fig. 1C-D). The average density of the sodium current was 216 ± 13 pA/pF (n = 97). No correlation between the current amplitude and the cell membrane capacitance was found (R2 = 0.01).


Dopaminergic modulation of the voltage-gated sodium current in the cochlear afferent neurons of the rat.

Valdés-Baizabal C, Soto E, Vega R - PLoS ONE (2015)

Effects of TTX, nickel and nifedipine on the INa.A) INa produced by voltage pulses from −110 mV to 50 mV in control conditions, during 100 nM TTX perfusion and 2 min after washout. In this and the following figures, only representative traces are shown. B) Current-voltage relationship in control conditions (black) and with TTX perfusion (blue). C) Current recording in control conditions and after coapplication of 10 μM nifedipine (Nfd) and 100 μM nickel. D) Current-voltage relationship in control conditions (black) and with Ni2+ plus nifedipine perfusion (red). In all traces, the dotted line indicates zero current.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4359166&req=5

pone.0120808.g001: Effects of TTX, nickel and nifedipine on the INa.A) INa produced by voltage pulses from −110 mV to 50 mV in control conditions, during 100 nM TTX perfusion and 2 min after washout. In this and the following figures, only representative traces are shown. B) Current-voltage relationship in control conditions (black) and with TTX perfusion (blue). C) Current recording in control conditions and after coapplication of 10 μM nifedipine (Nfd) and 100 μM nickel. D) Current-voltage relationship in control conditions (black) and with Ni2+ plus nifedipine perfusion (red). In all traces, the dotted line indicates zero current.
Mentions: The average capacitance of SGNs (n = 380) was 9 ± 0.5 pF. Some cells were identified as basal or apical cells, and no difference in membrane capacitance was found between cells from basal (8 ± 0.4 pF, n = 52) or apical portion of the cochlea (8 ± 0.3 pF, n = 85). The INa was blocked by TTX (Fig. 1A-B) and unaltered by the calcium channel antagonists nifedipine (10 μM) and nickel (100 μM) (Fig. 1C-D). The average density of the sodium current was 216 ± 13 pA/pF (n = 97). No correlation between the current amplitude and the cell membrane capacitance was found (R2 = 0.01).

Bottom Line: Recordings of the INa showed that DA receptor activation induced a significant inhibition of the peak current amplitude, leading to a significant decrease in cell excitability.The action of the D1- and D2-like receptors was shown to be mediated by a Gαs/AC/cAMP/PKA and Gαq/PLC/PKC pathways respectively.These results showed that DA receptor activation constitutes a significant modulatory input to SGNs, effectively modulating their excitability and information flow in the auditory pathway.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México.

ABSTRACT
The cochlear inner hair cells synapse onto type I afferent terminal dendrites, constituting the main afferent pathway for auditory information flow. This pathway receives central control input from the lateral olivocochlear efferent neurons that release various neurotransmitters, among which dopamine (DA) plays a salient role. DA receptors activation exert a protective role in the over activation of the afferent glutamatergic synapses, which occurs when an animal is exposed to intense sound stimuli or during hypoxic events. However, the mechanism of action of DA at the cellular level is still not completely understood. In this work, we studied the actions of DA and its receptor agonists and antagonists on the voltage-gated sodium current (INa) in isolated cochlear afferent neurons of the rat to define the mechanisms of dopaminergic control of the afferent input in the cochlear pathway. Experiments were performed using the voltage and current clamp techniques in the whole-cell configuration in primary cultures of cochlear spiral ganglion neurons (SGNs). Recordings of the INa showed that DA receptor activation induced a significant inhibition of the peak current amplitude, leading to a significant decrease in cell excitability. Inhibition of the INa was produced by a phosphorylation of the sodium channels as shown by the use of phosphatase inhibitor that produced an inhibition analogous to that caused by DA receptor activation. Use of specific agonists and antagonists showed that inhibitory action of DA was mediated both by activation of D1- and D2-like DA receptors. The action of the D1- and D2-like receptors was shown to be mediated by a Gαs/AC/cAMP/PKA and Gαq/PLC/PKC pathways respectively. These results showed that DA receptor activation constitutes a significant modulatory input to SGNs, effectively modulating their excitability and information flow in the auditory pathway.

Show MeSH
Related in: MedlinePlus