The amplitude and frequency of respiratory motor output are altered by different concentrations of nicotine in the brainstem spinal cord preparation from neonatal rats

Abstract

Nicotinic acetylcholine receptors (nAChRs) are a diverse and extensive group of ligand-gated channels that modulate fast synaptic transmission. Multiple nAChRs subtypes exist, each with potential differences in kinetics and sensitivities to agonists. nAChRs are found throughout the regions of the brainstem and spinal cord involved with the control of breathing, where they directly mediate the actions of acetylcholine and nicotine. In reduced neural preparations, nicotine can alter the amplitude and frequency of respiratory motor output. Multiple nAChR subtypes may exist within the respiratory network, each having different effects on the amplitude or frequency of respiratory motor output, however this possibility has not been thoroughly investigated. Here, respiratory motor bursting was recorded from the 4th cervical ventral root in brainstem spinal-cord preparations from rats at postnatal days 1–5. The frequency and amplitude of bursts were recorded at baseline, and during bath application of either 125 nM or 250 nM of nicotine (n=7 in each group). Results from these experiments show that both 125 nM and 250 nM nicotine increased the frequency of bursting (2-way ANOVA: Time, P=0.0003; Treatment, P=0.019; Interaction, P=0.14), however, while 250 nM nicotine caused a significant decrease in burst amplitude, 125 nM nicotine had no effect (2-way ANOVA: Time, P<0.0001; Treatment, P=0.032; Interaction, P=0.035). These data indicate that the frequency and amplitude responses to nicotine can be activated at different doses and suggest that multiple nAChR subtypes, with different sensitivity to nicotine, may exist within the respiratory neural network.