Ethanol effects on two types of voltage-activated calcium channels.
Ethanol has been shown to suppress calcium uptake into depolarized synaptosomes, to reduce the durations of calcium spikes in cultured cells and to reduce calcium conductances in invertebrate neurons. Voltage-activated calcium channels therefore appear to be an important target of ethanol action. However, the interactions of ethanol with specific types of calcium channels have yet to be defined. This study examined the effects of ethanol on two different populations of calcium channels in N1E-115 neuroblastoma and in NG108-15 neuroblastoma x glioma hybrid cells. Transient (type I) and long-lasting (type II) calcium channel currents were recorded with the whole-cell voltage clamp technique. At concentrations above 30 mM, ethanol reversibly suppressed both types of calcium channel currents, without changing the voltage dependence of activation. Concentration-response curves were essentially the same for type I and type II channels. Ethanol at concentrations of 100 and 300 mM blocked currents by approximately 15 and 40%, respectively. The voltage dependence of type I channel inactivation was not altered by ethanol concentrations as high as 300 mM, nor was there evidence of a use-dependent blocking action. The effects of ethanol on calcium channels were similar in NG108-15 cells; both channel types were blocked by ethanol at about the same concentrations as were effective in N1E-115 cells. Because ethanol interacts with opiate receptors in some systems, and leucine-enkephalin is known to block type II currents in NG108-15 cells, we examined whether the ethanol block of type II currents could be altered by naloxone.(ABSTRACT TRUNCATED AT 250 WORDS)
Twombly
D A
DA
Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois.
Herman
M D
MD
Kye
C H
CH
Narahashi
T
T
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007700:Kinetics; D009270:Naloxone / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D009270:Naloxone; D000431:Ethanol