Sex difference in neuronal loss induced by axotomy in the rat brain stem motor nuclei

Wang, Xueyong and Donald Robertson. Two types of actions of norepinephrine on identified auditory efferent neurons in rat brain stem slices. J. Neurophysiol. 78: 1800–1810, 1997. Whole cell voltage-clamp recordings were performed on auditory olivocochlear neurons in the ventral nucleus of the trapezoid body (VNTB) of brain stem slices from neonatal rats. Each neuron was identified by retrograde labeling with Fast Blue injected into the cochlea. Bath application of norepinephrine (NE; 1–10 μM) reversibly induced an inward current in 26 of 38 labeled neurons that were voltage clamped at −75 mV. This was responsible for the membrane depolarization to NE observed in current-clamp mode. The NE-induced inward current appeared to be more prominent at −55 mV than at −75 mV and reversed at around −100 mV. It was attenuated but not prevented by 20 mM tetraethylammonium, and it persisted when the perfusate contained 2 mM Cs+ or 100 μM Cd2+. However, the NE-induced inward current was attenuated to varying degrees in a zero-Ca2+ solution. Current-voltage plots revealed that NE caused a decrease in membrane K+ conductance. A suppression of voltage-gated Ca2+ currents by NE was also observed. The excitatory action of NE was blocked by the α-adrenoreceptor antagonist phentolamine. The α1-adrenoreceptor agonist phenylephrine had an effect similar to that of NE. In 6 of 38 labeled neurons, an inhibitory action of NE (1–10 μM) was observed that appeared to be due to an activation of an inwardly rectified K+ current, which caused hyperpolarization of resting membrane potentials in current-clamp mode. This inhibitory response was independent of external Ca2+ and was abolished by 2–5 mM Cs+ or 0.5 mM Ba2+ applied in the perfusate. The receptors involved in the inhibitory actions of NE are not clear. The effect was partially and reversibly blocked by propranolol (10 μM), a β-adrenoreceptor antagonist. However, isoprenaline (10 μM), a β-adrenoreceptor agonist, failed to induce any effect. On the other hand, the inhibitory effect was irreversibly blocked by pretreatment with phentolamine (5–10 μM). Phenylephrine (5–10 μM) had no effect.

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Substance P-Induced Inward Current in Identified Auditory Efferent Neurons in Rat Brain Stem Slices

Journal of Neurophysiology ◽

10.1152/jn.1998.80.1.218 ◽

1998 ◽

Vol 80 (1) ◽

pp. 218-229 ◽

Cited By ~ 15

Author(s):

Xueyong Wang ◽

Donald Robertson

Keyword(s):

Substance P ◽

Brain Stem ◽

Rat Brain ◽

Inward Rectifier ◽

Equilibrium Potential ◽

Inward Current ◽

Efferent Neurons ◽

Auditory Efferent ◽

Brain Stem Slices ◽

Stem Slices

Wang, Xueyong and Donald Robertson. Substance P-induced inward current in identified auditory efferent neurons in rat brain stem slices. J. Neurophysiol. 80: 218–229, 1998. The effects of substance P (SP) on whole cell currents were studied in neurons of the medial olivocochlear efferent system (MOCS) in the ventral nucleus of the trapezoid body (VNTB) of brain stem slices from neonatal rats. Each neuron was identified by retrograde labeling with Fast Blue injected into the cochlea. Bath application of SP (0.1–10 μM) reversibly induced an apparent inward current in 49 of 63 labeled neurons when voltage clamped at near resting voltages. This apparent inward current was consistent with the SP-induced membrane depolarization observed in current-clamp mode. The SP-induced change in current was dose dependent with a half-maximal response dose of 200 nM. It was mimicked by [Cys3,6, Tyr8, Pro9]-SP, a neurokinin (NK1) receptor selective agonist, whereas [Succinyl-Asp6, MePhe8]-SP 6–11 (Senktide), a NK3 receptor agonist, had no detectable effect. The SP effect was not blocked by 10-6 M tetrodotoxin (TTX) and persisted when the perfusate contained 30 mM tetraethylammonium (TEA) or 100 μM Cd2+ or was in a 0-Ca solution. In a TTX-containing solution, SP caused a voltage-dependent decrease of membrane conductance, and the SP-evoked current reversed at a potential at around −105 mV. The predicted K+ equilibrium potential was −93.8 mV under the experimental conditions. The SP-induced inward current was attenuated by 66% when the perfusate contained 3 mM Cs+. We conclude that the apparent inward current is partly caused by SP decreasing an outward current normally maintained by the inward rectifier K+ channels in these cells. In the presence of Cs solution in the recording pipette and with a perfusate containing 3 mM Cs+, 0.1 mM Cd2+ and 10-6 M TTX, a residual SP-induced inward current was observed at test voltages ranging from −120 to 40 mV. This subcomponent reversed its polarity at ∼20 mV. This inward current was reduced substantially (but not abolished) when all NaCl in the external solution was replaced by TEA-Cl. The results indicate that SP also opens an unknown cation channel, which the available data suggests may be relatively nonselective. The results suggest that MOCS neurons are subject to modulation by SP, which depolarizes the cell membrane by decreasing the activity of inward rectifier K+ channels as well as concurrently activating a separate cation conductance. It also was found that in MOCS neurons responsive to both SP and norepinephrine, the norepinephrine effect was abolished by TTX, suggesting that an interneuronal population excited by norepinephrine converges selectively onto SP-sensitive MOCS neurons in the VNTB.

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