title: Multiple conductances are modulated by 5-HT receptor subtypes in rat subthalamic nucleus neurons.
abstract: Firing patterns of subthalamic nucleus (STN) neurons influence normal and abnormal movements. The STN expresses multiple 5-HT receptor subtypes that may regulate neuronal excitability. We used whole-cell patch-clamp recordings to characterize 5-HT receptor-mediated effects on membrane currents in STN neurons in rat brain slices. In 80 STN neurons under voltage-clamp (-70 mV), 5-HT (30 microM) evoked inward currents in 64%, outward currents in 17%, and biphasic currents in 19%. 5-HT-induced outward current was caused by an increased K(+) conductance (1.4+/-0.2 nS) and was blocked by the 5-HT(1A) antagonist WAY 100135. The 5-HT-evoked inward current, which was blocked by antagonists at 5-HT(2C) and/or 5-HT(4) receptors, had two types of current-voltage (I-V) relations. Currents associated with the type 1 I-V relation showed negative slope conductance at potentials <-110 mV and were occluded by Ba(2+). In contrast, the type 2 I-V relation appeared linear and had positive slope conductance (0.64+/-0.11 nS). Type 2 inward currents were Ba(2+)-insensitive, and the reversal potential of -19 mV suggests a mixed cation conductance. In STN neurons in which 5-HT evoked inward currents, 5-HT potentiated burst firing induced by N-methyl-d-aspartate (NMDA). But in neurons in which 5-HT evoked outward current, 5-HT slowed NMDA-dependent burst firing. We conclude that 5-HT receptor subtypes can differentially regulate firing pattern by modulating multiple conductances in STN neurons.
authors: Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA.
authors: K-Z
authors: KZ
authors: Shen
authors: L B
authors: LB
authors: Kozell
authors: S W
authors: SW
authors: Johnson
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D018490:Serotonin Agents / Q000494:pharmacology; D020531:Subthalamic Nucleus / Q000166:cytology*
chemical_list: D011985:Receptors, Serotonin; D018490:Serotonin Agents; D012701:Serotonin
references: Brain Res. 1990 Apr 9;513(1):43-59
references: 2350684
references: Curr Med Chem. 2006;13(25):3069-81
references: 17073648
references: J Physiol. 1990 Apr;423:63-76
references: 1696989
references: Science. 1990 Sep 21;249(4975):1436-8
references: 2402638
references: Neuroscience. 1991;40(2):399-412
references: 1851255
references: Br J Pharmacol. 1992 Apr;105(4):973-9
references: 1324059
references: Neuroscience. 1992 Sep;50(2):345-53
references: 1279460
references: J Physiol. 1992 Sep;455:471-85
references: 1484360
references: Naunyn Schmiedebergs Arch Pharmacol. 1993 Jun;347(6):569-82
references: 8361548
references: J Physiol. 1993 Sep;469:387-405
references: 8271204
references: Brain Res Mol Brain Res. 1994 Apr;23(1-2):163-78
references: 8028479
references: J Neurophysiol. 1994 Aug;72(2):507-20
references: 7983515
references: Neuropharmacology. 1994 Mar-Apr;33(3-4):551-7
references: 7984294
references: J Neurosci. 1995 Jan;15(1 Pt 1):223-9
references: 7529825
references: J Comp Neurol. 1995 Jan 16;351(3):357-73
references: 7706547
references: Brain Res Brain Res Rev. 1995 Jan;20(1):128-54
references: 7711765
references: Neurosci Lett. 1995 Jun 2;192(1):17-20
references: 7675300
references: N Engl J Med. 1998 Oct 15;339(16):1105-11
references: 9770557
references: J Neurosci. 1998 Oct 15;18(20):8153-62
references: 9763462
references: Ann Neurol. 1998 Oct;44(4):622-8
references: 9778260
references: J Neurosci. 1999 Jan 15;19(2):599-609
references: 9880580
references: J Physiol. 1999 May 15;517 ( Pt 1):217-28
references: 10226161
references: Nature. 1999 Aug 12;400(6745):677-82
references: 10458164
references: J Neurophysiol. 2005 Mar;93(3):1145-57
references: 15738272
references: Neuroreport. 2000 Feb 7;11(2):267-70
references: 10674468
references: J Physiol. 2000 Jun 1;525 Pt 2:331-41
references: 10835037
references: Eur J Neurosci. 2000 Jul;12(7):2597-607
references: 10947834
references: Brain Res. 2001 Apr 27;899(1-2):142-7
references: 11311875
references: Pharmacol Biochem Behav. 2002 Apr;71(4):569-80
references: 11888548
references: Neuropharmacology. 2002 May;42(6):772-81
references: 12015203
references: Trends Neurosci. 2002 Oct;25(10):525-31
references: 12220881
references: Eur J Neurol. 2002 Nov;9 Suppl 3:1-6
references: 12464115
references: J Neurosci. 2003 Mar 1;23(5):1916-23
references: 12629196
references: Eur J Neurosci. 2004 Jan;19(2):346-55
references: 14725629
references: Eur J Neurosci. 2004 Mar;19(5):1296-304
references: 15016087
references: J Neurosci. 2004 May 19;24(20):4807-17
references: 15152041
references: Nat Neurosci. 2004 Jun;7(6):587-8
references: 15146189
references: Neurosci Lett. 1985 Dec 18;62(3):305-9
references: 2419795
references: Brain Res. 1987 Oct 13;423(1-2):347-52
references: 3119155
references: J Physiol. 1987 Dec;394:99-124
references: 3443977
references: J Physiol. 1989 Oct;417:1-12
references: 2621587
references: Neuroscience. 1996 May;72(1):117-28
references: 8730711
references: Brain. 1996 Oct;119 ( Pt 5):1717-27
references: 8931592
references: Eur J Neurosci. 1996 Dec;8(12):2591-8
references: 8996808
references: Brain Res. 1997 Jan 16;745(1-2):283-92
references: 9037420
references: J Neurophysiol. 1997 Jun;77(6):2910-24
references: 9212246
references: J Physiol. 1998 Apr 1;508 ( Pt 1):67-81
references: 9490818
references: J Neurosci. 2005 Jul 6;25(27):6304-15
references: 16000620
references: Neuropharmacology. 2005 Dec;49(8):1228-34
references: 16229866
references: Trends Neurosci. 1990 Jul;13(7):281-5
references: 1695404