Characterization of outward currents induced by 5-HT in neurons of rat dorsolateral septal nucleus.

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 microM), a selective 5-HT(1A) receptor agonist, also produced outward currents with three types of voltage dependency. Ba(2+) (100 microM) 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 Ba(2+) (100 microM) 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 microM) and guanosine-5'-O-(2-thiodiphosphate) (5 mM), blockers of G protein, irreversibly depressed I(5-HT). Protein kinase C (PKC) 19-36 (20 microM), 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 microM) and adenosine 3',5'-cyclic monophosphothioate Rp-isomer (300 microM), protein kinase A inhibitors, did not depress I(5-HT). Phorbol 12-myristate 13-acetate (10 microM), 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.