Enhancement of gamma-aminobutyric acid-activated chloride channel currents by lanthanides in rat dorsal root ganglion neurons.
Lanthanum was previously reported to potentiate the GABA-induced chloride currents reversibly by acting at a distinct site on the GABAA receptor-channel complex (Ma and Narahashi, 1993). We now report that all other lanthanides tested enhanced the GABA responses with greater efficiencies and produced inward currents by themselves. The rank order of efficacies of lanthanides to potentiate the GABA responses and to generate currents correlated inversely with the hydrated ionic radii of these ions. The GABA-induced currents were recorded from the rat dorsal root ganglion neurons in primary culture by the whole-cell patch-clamp technique. Lanthanides at 1 mM reversibly potentiated the GABA responses (times of control): lutetium (Lu3+) 12.4 +/- 0.1 > erbium (Er3+) 11.4 +/- 0.2 > terbium (Tb3+) 9.3 +/- 0.5 > europium (Eu3+) 5.4 +/- 0.4 > neodymium (Nd3+) 4.1 +/- 0.2 > cerium (Ce3+) 3.3 +/- 0.2 > lanthanum (La3+) 2.4 +/- 0.2 (n = 10). The enhancing effect of Tb3+ was dose dependent, with an EC50 356 +/- 12 microM (n = 10), and weakly voltage dependent, increasing with hyperpolarization. The amplitudes of currents induced by various lanthanides (1 mM) were (percentage of 10 microM GABA-induced current) Lu3+ 101 +/- 8 > Er3+ 57 +/- 8 > Tb3+ 33 +/- 3 > Eu3+ 20 +/- 2 > Nd3+ 14 +/- 2 approximately Ce3+ 13 +/- 0.6 > La3+ 10 +/- 0.2 (n = 4). Tb3+ reversibly induced currents in a dose-dependent manner with an EC50 of 863 +/- 0 microM (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)
Ma
J Y
JY
Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois 60611.
Narahashi
T
T
D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D002478:Cells, Cultured; D002707:Chlordiazepoxide / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004553:Electric Conductivity / Q000187:drug effects; D005727:Ganglia, Spinal / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D008674:Metals, Rare Earth / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010406:Penicillins / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013725:Terbium / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001640:Bicuculline; D002707:Chlordiazepoxide; D018118:Chloride Channels; D007473:Ion Channels; D008674:Metals, Rare Earth; D010406:Penicillins; D010424:Pentobarbital; D010852:Picrotoxin; D013725:Terbium; D015032:Zinc; D005680:gamma-Aminobutyric Acid