The Journal of Neurophysiology Vol. 85 No. 4 April 2001, pp. 1453-1460
Copyright ©2001 by the American Physiological Society

Characterization of Outward Currents Induced by 5-HT in Neurons of Rat Dorsolateral Septal Nucleus

Department of Physiology, Kurume University School of Medicine, Kurume 830-0011, Japan

Yamada, Kei, Hiroshi Hasuo, Masaru Ishimatsu, and Takashi Akasu. Characterization of Outward Currents Induced by 5-HT in Neurons of Rat Dorsolateral Septal Nucleus. J. Neurophysiol. 85: 1453-1460, 2001. Properties of the 5-hydroxytryptamine (5-HT)-induced current (I_5-HT) were examined in neurons of rat dorsolateral septal nucleus (DLSN) by using whole cell patch-clamp techniques. I_5-HT was associated with an increase in the membrane conductance of DLSN neurons. The reversal potential of I_5-HT was 93 ± 6 (SE) mV (n = 7) in the artificial cerebrospinal fluid (ACSF) and was changed by 54 mV per decade change in the external K⁺ concentration, indicating that I_5-HT is carried exclusively by K⁺. Voltage dependency of the K⁺ conductance underlying I_5-HT was investigated by using current-voltage relationship. I_5-HT showed a linear I-V relation in 63%, inward rectification in 21%, and outward rectification in 16% of DLSN neurons. (±)-8-Hydroxy-dipropylaminotetralin hydrobromide (30 µM), a selective 5-HT_1A receptor agonist, also produced outward currents with three types of voltage dependency. Ba²⁺ (100 µM) blocked the inward rectifier I_5-HT but not the outward rectifier I_5-HT. In I_5-HT with linear I-V relation, blockade of the inward rectifier K⁺ current by Ba²⁺ (100 µM) unmasked the outward rectifier current in DLSN neurons. These results suggest that I_5-HT with linear I-V relation is the sum of inward rectifier and outward rectifier K⁺ currents in DLSN neurons. Intracellular application of guanosine-5'-O-(3-thiotriphosphate) (300 µM) and guanosine-5'-O-(2-thiodiphosphate) (5 mM), blockers of G protein, irreversibly depressed I_5-HT. Protein kinase C (PKC) 19-36 (20 µM), a specific PKC inhibitor, depressed the outward rectifier I_5-HT but not the inward rectifier I_5-HT. I_5-HT was depressed by N-ethylmaleimide, which uncouples the G-protein-coupled receptor from pertussis-toxin-sensitive G proteins. H-89 (10 µM) and adenosine 3',5'-cyclic monophosphothioate Rp-isomer (300 µM), protein kinase A inhibitors, did not depress I_5-HT. Phorbol 12-myristate 13-acetate (10 µM), an activator of PKC, produced an outward rectifying K⁺ current. These results suggest that both 5-HT-induced inward and outward rectifying currents are mediated by a G protein and that PKC is probably involved in the transduction pathway of the outward rectifying I_5-HT in DLSN neurons.