Nicotinic modulation of area postrema neuronal excitability in rat brain slices.
We investigated the functions of nicotinic receptor activation on area postrema neurons by making whole-cell recordings in rat brainstem slices. Excitatory responses to nicotine application were found in approximately 78% (35/45) of all cells tested. Responsive cells included both the cells that display the hyperpolarization-activated cation current (I(h)) and cells that do not display I(h). An inhibitory effect of nicotine was never seen. Current-clamp recordings showed the nicotine-induced depolarization of a cell's membrane potential that could be sufficient to cause spontaneous firing. In voltage-clamp recordings, many cells showed nicotine-induced inward currents (18.3+/-3.2 pA, n=6) that persisted during pharmacological blockade of synaptic transmission (e.g., zero [Ca(2+)](out) and 5 mM [Mg(2+)](out), n=6/8). Other two cells, however, showed increases in the frequency of excitatory postsynaptic currents (EPSCs), which were blocked by CNQX (n=2/8). We analyzed miniature EPSCs (mEPSCs) recorded from cells that showed no inward currents but marked increases in the frequency of mEPSCs (0.8+/-0.2 to 4.8+/-1.7 Hz, n=4) during nicotine application. Nicotine augmented mEPSC amplitude (n=4); however, amplitude distribution was not significantly changed in two of four cells tested. We conclude that nicotinic receptors in the rat area postrema can excite cells via (1) a direct post- and/or extrasynaptic mechanism; and (2) an indirect enhancement of glutamate release.
Funahashi
Makoto
M
Department of Oral Physiology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8525, Japan. mfuna@md.okayama-u.ac.jp
Mitoh
Yoshihiro
Y
Matsuo
Ryuji
R
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D031608:Area Postrema / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D013779:Tetrodotoxin; D009538:Nicotine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione