Noncholinergic actions of atropine on GABAergic synaptic transmission in the subfornical organ of rat slice preparations.
Actions of atropine on GABAergic inhibitory postsynaptic currents to neurons in the subfornical organ, which is a circumventricular organ, were studied by using rat slice preparations with whole-cell clamp recordings. Atropine at 0.01-1 microM antagonized the decreased frequency of Inhibitory postsynaptic currents by carbachol (Xu et al., Am. J. Physiol. Integr. Comp. Physiol. 280, R1657-R1664, 2001). It acted as a muscarinic antagonist at relatively low concentrations. Although the low concentrations of atropine did not change frequency and amplitude of the inhibitory postsynaptic currents, atropine at 10 microM to 1 mM did decrease them in a dose-dependent manner. Glutamatergic excitatory postsynaptic currents were not influenced by atropine at 100 microM. Atropine at 100 microM suppressed GABA- and muscimol-induced outward currents, but not kainic acid-induced inward currents. In addition, decrease of membrane conductance and induction of inward currents by 100 microM of atropine at a holding membrane potential, -51 mV, were found in subfornical organ neurons. From voltage-current curves, a mean reversal potential was estimated to be -65.9 +/- 3.7 mV, near to an equilibrium potential of chloride channels. These imply that atropine at 100 microM suppresses openings of chloride channels. Taken together, it is suggested that, while atropine at low concentrations has an antagonistic action on muscarinic responses, atropine at high concentrations suppresses GABAergic synaptic transmission in subfornical organ neurons. These findings may be of considerable value in understanding the central mechanisms of extraordinary drinking behavior in atropine intoxication.
Xu
Sheng-Hong
SH
Department of Physiology, Kyushu Dental College, Kokurakitaku, Kitakyushu 803-8580, Japan.
Ono
Kentaro
K
Honda
Eiko
E
Inenaga
Kiyotoshi
K
D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D013356:Subfornical Organ / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D018757:GABA Modulators; D018727:Muscarinic Antagonists; D001285:Atropine