Alcohol is classified pharmacologically as a central nervous system depressant. The cellular mechanisms that underlie this alcohol-induced depression of nervous system excitability, however, are poorly understood. This project investigated the intrinsic mechanisms involved in the regulation of nerve cell excitability and the effects of ethanol on those mechanisms. Whole-cell patch-clamp recording in combination with axonal tracing techniques were used to examine the electrical properties of rat dorsal root ganglion (DRG) neurons. The majority of neurons were small (70%), and expressed high-threshold tetrodotoxin (TTX)-resistant Na+ channels and slowly-inactivating K+ channels (K-A). The large-sized neurons had low-threshold TTX-sensitive Na+ channels and fast-inactivating K-A channels. Half-maximal conductances for activation of TTX-resistant and TTX-sensitive Na+ currents were -10.3 and -25.3 mV. TTX-resistant and TTX-sensitive Na+ currents were half-inactivated at -25.3 and -56 mV. In TTX-resistant neurons, transient K+ current (I-A) had half-maximal conductance at -40.8 mV, was half-inactivated at -77.5 mV, and exhibited a slower decay constant (tau, 240 ms) than I-A current in TTX-sensitive neurons (tau, 20 ms). Na+ and K+ currents were similarly characterized in rat major pelvic ganglion (MPG) neurons. Na+ current was reversibly blocked by 1 uM TTX. Na+ conductance reached half-maximal activation at -21.5 mM, and was half-maximally inactivated at -57.5 mV. A fast-transient I-A current was half-maximally activated at -21.2 mV, and half-maximally inactivated at -76.5 mV. A delayed K+ current was reduced by 25-35% by the bath application of Cd2+ or 0 Ca2; 4-AP (2 mM) suppressed I-A current by 75% and delayed K+ current by 60%; and TEA (10 mM) suppressed delayed K+ current by 90% and I-A current by 16%. The results indicate that MPG neurons have a TTX-sensitive Na+ current, and three distinct types of K+ currents: I-A, Ca2+-activated, and delayed rectifier. The effect of ethanol was tested on voltage-gated ion channels in several types of neurons and it was found to have little or no effect on channel function in a pharmacologic concentration range (5-100 mM).
| 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 |
