Lead modulation of the neuronal nicotinic acetylcholine receptor in PC12 cells.
Lead is known to modulate several ligand- and voltage-gated ion channels, including the nicotinic acetylcholine receptor (AChR) channel. We examined the effects of lead on the nicotinic AChR in rat clonal phaeochromocytoma PC12 cells using whole-cell and single-channel patch-clamp techniques to clarify the detailed mechanism of action. Lead suppressed acetylcholine-induced currents in a dose-dependent manner with an EC50 value of 37 microM and a Hill coefficient of 0.82. At the single-channel level, 1-10 microM lead shortened the opening and burst durations, and increased the duration of mean closed time. The open probability was significantly decreased by lead. These changes of single-channel kinetics result in a significant decrease in the total charge carried through the open AChR channels explaining the suppressive effect of lead on acetylcholine-induced whole-cell currents.
Nagata
K
K
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, IL 60611, USA.
Huang
C S
CS
Song
J H
JH
Narahashi
T
T
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D007854:Lead / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*
D011978:Receptors, Nicotinic; D007854:Lead; D000109:Acetylcholine