Two types of actions of norepinephrine on identified auditory efferent neurons in rat brain stem slices

Abstract

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 microM) 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 microM 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 alpha-adrenoreceptor antagonist phentolamine. The alpha1-adrenoreceptor agonist phenylephrine had an effect similar to that of NE. In 6 of 38 labeled neurons, an inhibitory action of NE (1-10 microM) 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 microM), a beta-adrenoreceptor antagonist. However, isoprenaline (10 microM), a beta-adrenoreceptor agonist, failed to induce any effect. On the other hand, the inhibitory effect was irreversibly blocked by pretreatment with phentolamine (5-10 microM). Phenylephrine (5-10 microM) had no effect.