Differential effects of thiopental on neuronal nicotinic acetylcholine receptors and P2X purinergic receptors in PC12 cells.
BACKGROUND
PC12 cells, derived from rat pheochromocytoma, express neuronal nicotinic acetylcholine receptors (nAchRs) and P2X purinergic receptors, both of which resemble the receptors in postganglionic sympathetic neurons. The former is the established and the latter is the putative receptor to mediate fast synaptic transmission. The authors investigated effects of thiopental on these two ligand-gated ion channels.


METHODS
Whole cell currents were recorded in PC12 cells without treatment of nerve growth factor, using conventional whole cell patch clamp technique. Nicotine or adenosine triphosphate (ATP) 30 microM was applied for 4-5 s in the absence or presence of thiopental 3-300 microM.


RESULTS
Nicotine induced the rapidly decaying inward current at -60 mV, which exhibited the characteristics of the neuronal nAchR-mediated current. Thiopental inhibited the nicotine-induced inward current and accelerated the current decay in a dose-dependent manner, resulting in the greater effects on the steady current than the peak current. IC50s for the peak and steady current were 56.7 and 7.4 microM, when the anesthetic was coapplied with nicotine. Thiopental's inhibition was not associated with a change in the reversal potential and was voltage-independent at membrane potential of -30 to -70 mV. Most of thiopental's effects seemed to require channel opening. In contrast to the nicotine-induced current, thiopental had little effect on the current elicited by ATP.


CONCLUSIONS
Thiopental, whose reported EC50 for general anesthesia is 25 microM, inhibited the neuronal nAchR-mediated current but not the P2X receptor-mediated response in PC12 cells at clinically relevant concentrations. Inhibition may result in suppression of synaptic transmission in sympathetic ganglia.
Andoh
T
T
Department of Anesthesiology, Yokohama City University School of Medicine, Yokohama, Japan. tandoh@med.yokohama-cu.ac.jp
Furuya
R
R
Oka
K
K
Hattori
S
S
Watanabe
I
I
Kamiya
Y
Y
Okumura
F
F
D000255:Adenosine Triphosphate / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D008564:Membrane Potentials / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects*; D018048:Receptors, Purinergic P2 / Q000187:drug effects*; D013874:Thiopental / Q000494:pharmacology*
D018686:Anesthetics, Intravenous; D011978:Receptors, Nicotinic; D018048:Receptors, Purinergic P2; D009538:Nicotine; D000255:Adenosine Triphosphate; D013874:Thiopental