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 voltage-dependent membrane ion channels in neuronal precursor cells. Precursor cells from the anterior subventricular zone (SVZa) of neonatal rat forebrain express neuron-specific markers and divide while migrating along the path to the olfactory bulb, where they differentiate into granule and periglomerular interneurons. SVZa cells also express neuron-specific tublin and divide in vitro. Voltage-dependent potassium currents were studied using whole-cell patch-clamp recording in SVZa cells isolated from newborn rats and cultured for 1 day. A-type potassium current (I-K[A]) was recorded in the presence of 300 nM tetrodotoxin and 20 mM tetraethylammonium (TEA); it was identified by its properties of steady-state half-inactivation (-90 mV) and rapid recovery from inactivation (20 ms at -130 mV). Inactivation of I-K[A] was voltage-independent and had a time-constant of 15 ms. The second potassium current identified resembled a delayed rectifier (I-K[DR]) by inactivating slowly over several seconds and being blocked reversibly by external TEA (IC50 4.1 mM). I-K[DR] exhibited steady-state half-inactivation of -50 mV and sigmoidal activation kinetics, with time-constants ranging from 11 ms at -40 mV to 1.5 ms at 100 mV. Although SVZa cells undergo division in culture, their properties resemble those of postmitotic cerebellar granule neurons. Future experiments are planned to study the effect of alcohol on these currents.
| 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 |
