Although it is well known that the administration of ethanol can affect nervous system excitability, the cellular basis of such actions is poorly understood. The objective of this project was to characterize the mechanisms regulating nerve cell excitability and the effects of ethanol on those mechanisms. Excitability mechanisms were characterized by two electrophysiological methods: (i) wholecell patch-clamp recording of acutely isolated adult rat nodose or superior cervical ganglion cells; and (ii) single electrode voltage-clamp recording of CA3 pyramidal neurons in hippocampal slice. In nodose ganglion neurons, two sodium currents were characterized: a tetrodotoxin (TTX)-sensitive sodium current with a rapid time course, and a TTX-resistant sodium current with a slower time course. In addition, two calcium currents were characterized, a transient and a sustained calcium current. In the sympathetic neurons, three potassium currents were isolated, a transient potassium current, a sustained calcium-sensitive potassium current, and a delayed rectifier current. In hippocampal pyramidal neurons, a transient and a sustained calcium current, and a calcium-activated potassium current have been characterized. Moreover, it has been found that the calcium current and the calcium-activated potassium current are inhibited by activation of muscarinic receptors. The effect of ethanol is being studied on these ion currents. The significance of the project lies in the fact that the identification of the mechanisms involved in nerve cell excitability and the investigation of the action of ethanol on those mechanisms holds the promise of increasing our understanding of the cellular basis of ethanol's actions in the nervous system.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Intramural Research (Z01)
Project #
1Z01AA000480-03
Application #
3823002
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Alcohol Abuse and Alcoholism
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Li, Chao-Ying; Xiong, Ke-Ming; Wu, Yu-Xiang et al. (2013) Conserved extracellular cysteines differentially regulate the potentiation produced by Zn2+ in rat P2X4 receptors. Eur J Pharmacol 707:11-6
Koyama, Susumu; Kanemitsu, Yoshio; Weight, Forrest F (2005) Spontaneous activity and properties of two types of principal neurons from the ventral tegmental area of rat. J Neurophysiol 93:3282-93