Effects of 5-Hydroxytryptamine on Neuronal Activities in the Rat Dorsolateral Septal Nucleus.
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The ionic channels and signal transduction pathways underlying the 5-hydroxytryptamine (5-HT)-induced hyperpolarization in neurons of the rat dorsolateral septal nucleus (DLSN) were examined by using intracellular and voltage-clamp recording techniques . Application of 5-HT (1-5O μM) caused a hyperpolarizing response associated with a decreased membrane resistance in DLSN neurons. The hyperpolarization induced by 5-HT was blocked by Ba<SUP>2+</SUP> (1 mM) but not by tetraethylammonium (TEA, 3 mM), glibenclamide (100 μM) and extracellular Cs<SUP>+</SUP> (2 mM) . 8-Hydroxydi-n-propylamino tetralin (8-OH-DPAT; 3 μM), a selective agonist for the 5-HT<SUB>1A</SUB> receptor, mimicked 5-HT in producing the hyperpolarizatio. The 5-HT hyperpolarization was blocked by NAN-190 (5 μM), a 5-HT<SUB>1A</SUB> receptor antagonist. CP93129 (100 μM), a 5-HT<SUB>1B</SUB> receptor agonist, and L-694-247 (100 μM), a 5-HT<SUB>1B/1D</SUB> receptor agonist, also produced hyperpolarizing responses. The order of agonist potency was 8-OH-DPAT>> CP93129≥L-694-247. (±)-2, 5-Dimethoxy-4-iodoamphetamine hydrochloride (DOl, 100 μM), a 5-HT<SUB>2</SUB> receptor agonist, and RS67333 (100 μM), a 5-HT<SUB>4</SUB> receptor agonist, caused no hyperpolarizing response. The voltage-clamp study showed that 5-HT caused an outward current (l<SUB>5-HT</SUB>) in a concentration-dependent manner. l<SUB>5-HT</SUB> was associated with an increased membrane conductance. l<SUB>5-HT</SUB> reversed the polarity at the equilibrium potential for K<SUP>+</SUP> calculated by the Nernst equation. l<SUB>5-HT</SUB> showed inward rectification at membrane potentials more negative than -70 mV. Ba<SUP>2+</SUP> (100 μM) blocked the inward rectifier K<SUP>+</SUP> current induced by 5-HT. l<SUB>5-HT</SUB> was irreversibly depressed by intracellular application of guanosine 5'-O-(3-thiotriphosphate)(GTP-γS) but not by guanosine 5'-O-(2-thiodiphosphate) (GDPβS). These results suggest that in rat DLSN neurons activation of 5-HT<SUB>1A</SUB> receptors causes a hyperpolarizing response by activating mainly the inward rectifier K<SUP>+</SUP> channels through a GTP-binding protein.
- 久留米大学医学部 The Kurume Medical Journal 編集部の論文
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