PMID- 9084603
OWN - NLM
STAT- MEDLINE
DCOM- 19970613
LR  - 20171213
IS  - 0022-3077 (Print)
IS  - 0022-3077 (Linking)
VI  - 77
IP  - 3
DP  - 1997 Mar
TI  - Effects of serotonin on caudal raphe neurons: inhibition of N- and P/Q-type 
      calcium channels and the afterhyperpolarization.
PG  - 1362-74
AB  - We characterized whole cell barium currents through calcium channels and 
      investigated the effects of serotonin (5-HT) on calcium channel currents and 
      firing behavior in visualized caudal raphe neurons of the neonatal rat in brain 
      stem slices (n = 201). A subpopulation of recorded neurons was recovered after 
      staining for tryptophan hydroxylase (TPH), the 5-HT synthesizing enzyme (n = 21); 
      of those cells, 86% were TPH immunoreactive, suggesting that the majority of 
      recorded neurons was serotonergic. Calcium channel currents began to activate at 
      about -40 mV in caudal raphe neurons and showed a peak amplitude of 952.2 +/- 
      144.2 (SE) pA at -10 mV. A small low-voltage activated current was also observed 
      (approximately 22 pA). Calcium channel currents were potently inhibited by 
      bath-applied 5-HT in most cells tested (approximately 90%). The EC50 for 
      inhibition of calcium current by 5-HT was 0.1 microM; a saturating concentration 
      (1.0 microM) blocked approximately 40% of the current evoked at 0 mV from a 
      holding potential of -70 mV (n = 101). Current inhibition was associated with a 
      slowing of activation kinetics and a shift in the peak of the current-voltage 
      relationship, and was partially relieved by strong depolarizations. Current 
      inhibition by 5-HT was mimicked by 8-OH-DPAT, a specific 5-HT1A agonist, and 
      blocked by the 5-HT1a antagonists NAN 190 and (+) WAY 100135, but was unaffected 
      by ketanserin, a 5-HT2A/C antagonist. omega-Conotoxin GVIA (omega-CgTx)-sensitive 
      N-type channels and omega-agatoxin IVA (omega-AgaIVA)-sensitive P/Q-type channels 
      together accounted for most of the calcium current (36 and 37%, respectively). 
      Nimodipine had no effect on the calcium current, indicating that caudal raphe 
      neurons do not express dihydropyridine-sensitive L-type currents. A substantial 
      residual current (27%) remained after application of omega-CgTx, omega-AgaIVA, 
      and nimodipine. Most of the 5-HT-sensitive calcium current was blocked by 
      omega-CgTx and omega-AgaIVA; 5-HT had little effect on the residual current. 
      Inhibition of calcium current by 5-HT was irreversible when GTP gamma S, a 
      nonhydrolyzable guanosine 5'-triphosphate (GTP) analogue, was substituted for GTP 
      in the pipette. In addition, the effects of 5-HT were blocked by pretreating 
      slices with pertussis toxin (PTX). Together these data indicate that inhibition 
      of N- and P/Q-type calcium current in serotonergic caudal raphe neurons is 
      mediated by a 5-HT1A receptor via PTX-sensitive G proteins. Under current clamp, 
      calcium channel toxins (omega-CgTx and omega-AgaIVA) and 5-HT each caused a 
      decrease in the spike afterhyperpolarization and enhanced the repetitive firing 
      response to injected current. The similar effects of 5-HT and the calcium channel 
      toxins on firing behavior suggest that those effects of 5-HT were secondary to 
      inhibition of N- and P/Q-type calcium channels.
FAU - Bayliss, D A
AU  - Bayliss DA
AD  - Department of Pharmacology, University of Virginia, Charlottesville 22908, USA.
FAU - Li, Y W
AU  - Li YW
FAU - Talley, E M
AU  - Talley EM
LA  - eng
GR  - R01 NS033583/NS/NINDS NIH HHS/United States
GR  - NS-33583/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurophysiol
JT  - Journal of neurophysiology
JID - 0375404
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels)
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Virulence Factors, Bordetella)
RN  - 24GP945V5T (Barium)
RN  - 333DO1RDJY (Serotonin)
RN  - EC 2.4.2.31 (Pertussis Toxin)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Barium/metabolism
MH  - Calcium Channel Blockers/*pharmacology
MH  - Calcium Channels/drug effects/*metabolism
MH  - Electrophysiology
MH  - GTP-Binding Proteins/metabolism
MH  - In Vitro Techniques
MH  - Membrane Potentials/drug effects/physiology
MH  - Neurons/drug effects/metabolism
MH  - Patch-Clamp Techniques
MH  - Pertussis Toxin
MH  - Raphe Nuclei/cytology/*drug effects
MH  - Rats
MH  - Receptors, Serotonin/drug effects
MH  - Serotonin/metabolism/*pharmacology
MH  - Virulence Factors, Bordetella/pharmacology
EDAT- 1997/03/01 00:00
MHDA- 1997/03/01 00:01
CRDT- 1997/03/01 00:00
PHST- 1997/03/01 00:00 [pubmed]
PHST- 1997/03/01 00:01 [medline]
PHST- 1997/03/01 00:00 [entrez]
AID - 10.1152/jn.1997.77.3.1362 [doi]
PST - ppublish
SO  - J Neurophysiol. 1997 Mar;77(3):1362-74. doi: 10.1152/jn.1997.77.3.1362.