title: Effects of prenatal ethanol exposure on voltage-dependent calcium entry into neonatal whole brain-dissociated neurons.
abstract: The effect of prenatal ethanol exposure on voltage-dependent calcium entry into neonatal-dissociated neurons was studied. Dissociated whole brain cells were isolated from neonates of prenatally ethanol-treated (ET), pair-fed (PF) control, and ad libitum (AL) control groups and loaded with fura-2. Prenatal ethanol exposure resulted in a significant reduction of calcium entry into K(+)-depolarized cells, compared with AL and PF control treatments. Initially, in dissociated cells from AL control animals, it was found that nifedipine (1 microM), omega-agatoxin (100 nM), and omega-conotoxin (500 nM), to a much lesser extent, significantly inhibited the 45 mM KCl-stimulated calcium entry. To determine the inhibitory action of prenatal ethanol exposure on N-, P-, and L-type voltage-dependent calcium channels, treatment of neonatal-dissociated neurons with different combinations of omega-conotoxin, omega-agatoxin, and nifedipine, respectively, was compared in the prenatal ethanol and control treatment groups. The inhibition of K(+)-stimulated increase in calcium entry by prenatal ethanol exposure was significantly less in the presence or absence of single antagonist conditions (ET < AL and PF). There was no apparent interaction of ethanol exposure and antagonist condition. However, the reduced calcium entry after prenatal ethanol exposure was superseded by the stronger inhibition in dual and triple antagonist conditions. The magnitude of the calcium response inhibition by the antagonist combinations was similar among the ET, PF, and AL groups. Thus, these results suggest that prenatal ethanol exposure decreases voltage-dependent calcium entry into neonatal-dissociated neurons in a manner that does not seem to involve the selective inhibition of any individual N-, P-, or L-type calcium channel.
authors.affiliation: Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin 78712-1074, USA.
authors.forename: Y H
authors.initials: YH
authors.lastname: Lee
authors.forename: K
authors.initials: K
authors.lastname: Spuhler-Phillips
authors.forename: P K
authors.initials: PK
authors.lastname: Randall
authors.forename: S W
authors.initials: SW
authors.lastname: Leslle
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011188:Potassium / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011188:Potassium; D002118:Calcium