441 - Ethanol causes dose dependent alterations of BK distribution in Lipid Rafts of the Nucleus tractus solitarius of rat pups
Monday, April 28, 2025
7:00am – 9:15am HST
Publication Number: 441.5063
Mrinaj Janampalli, Case Western Reserve University School of Medicine, Cleveland, OH, United States; Anushka Shah, Case Western Reserve University School of Medicine, Cleveland, OH, United States; Catherine Mayer, UH Rainbow Babies & Children's Hospital, Cleveland, OH, United States; Peter M. MacFarlane, Case Western Reserve University School of Medicine, Cleveland, OH, United States; Cynthia Bearer, UH Rainbow Babies & Children's Hospital/Case Western Reserve University, Cleveland, OH, United States
Research Assistant Case Western Reserve University School of Medicine Cleveland, Ohio, United States
Background: Apnea of prematurity (AOP) is a common respiratory morbidity in preterm infants, which can be exacerbated upon exposure to ethanol (EtOH). Preterm infants in the NICU can be routinely exposed to EtOH via several medications, as EtOH is used in some as a solvent for effective administration. The nucleus tractus solitarius (NTS) is an integral component of the neural pathways modulating respiratory drive and apnea. The large conductance calcium- and voltage-activated K+ channel (BK) that regulates the neuronal activity of the NTS are lipid raft (LR) associated proteins. We have previously shown that two doses of 2.5 g/kg/day 2 hours apart on postnatal day (P)5 decreases ventilatory responses to hypoxia and hypercapnia on P6 as measured by whole-body plethysmography in female animals and redistributes BK out of LR in the NTS. Objective: We investigated the dose-response relationship between EtOH exposure and the distribution of BK in LR of the NTS. Design/Methods: From postnatal day (P) 3 to P5, Sprague Dawley rat pups were gavaged with intralipid mixed with EtOH to provide 0.25, 0.5, 1, and 2 g/kg/day of EtOH or intralipid mixed with sucrose. The NTS was dissected, homogenized and lipid rafts isolated into LR and non-LR pools. The proportion of each channel within the LR pool was determined. Results: The 2.0g/kg/day group had the highest amount of BK redistribution with 36.2% being found outside of lipid rafts compared to 6.9% in the control group. The lowest dose with a significant difference from control was 0.5g/kg/day with 17.9%. (p < 0.05, ANOVA Tukey post hoc).
Conclusion(s): The results suggest that lower, more chronic exposure to EtOH may impair respiratory drive due to disruption of BK signaling in the NTS. This may have widespread implications for preterm infants in the NICU being administered EtOH containing medications.
