PMID- 9862898
OWN - NLM
STAT- MEDLINE
DCOM- 19990210
LR  - 20171213
IS  - 0022-3077 (Print)
IS  - 0022-3077 (Linking)
VI  - 80
IP  - 6
DP  - 1998 Dec
TI  - Opioid-activated postsynaptic, inward rectifying potassium currents in whole cell 
      recordings in substantia gelatinosa neurons.
PG  - 2954-62
AB  - Opioid-activated postsynaptic, inward rectifying potassium currents in whole cell 
      recordings in substantia gelatinosa neurons. J. Neurophysiol. 80: 2954-2962, 
      1998. Using tight-seal, whole cell recordings from isolated transverse slices of 
      hamster and rat spinal cord, we investigated the effects of the mu-opioid agonist 
      (-Ala2, N-Me-Phe4,Gly5-ol)-enkephalin (DAMGO) on the membrane potential and 
      conductance of substantia gelatinosa (SG) neurons. We observed that bath 
      application of 1-5 microM DAMGO caused a robust and repeatable hyperpolarization 
      in membrane potential (Vm) and decrease in neuronal input resistance (RN) in 60% 
      (27/45) of hamster neurons and 39% (9/23) of rat neurons, but significantly only 
      when ATP (2 mM) and guanosine 5'-triphosphate (GTP; 100 microM) were included in 
      the patch pipette internal solution. An ED50 of 50 nM was observed for the 
      hyperpolarization in rat SG neurons. Because G-protein mediation of opioid 
      effects has been shown in other systems, we tested if the nucleotide requirement 
      for opioid hyperpolarization in SG neurons was due to G-protein activation. GTP 
      was replaced with the nonhydrolyzable GTP analogue 
      guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S; 100 microM), which enabled 
      DAMGO to activate a nonreversible membrane hyperpolarization. Further, 
      intracellular application of guanosine-5'-O-(2-thiodiphosphate) (GDP-beta-S; 500 
      microM), which blocks G-protein activation, abolished the effects of DAMGO. We 
      conclude that spinal SG neurons are particularly susceptible to dialysis of GTP 
      by whole cell recording techniques. Moreover, the depletion of GTP leads to the 
      inactivation of G-proteins that mediate mu-opioid activation of an 
      inward-rectifying, potassium conductance in these neurons. These results explain 
      the discrepancy between the opioid-activated hyperpolarization in SG neurons 
      observed in previous sharp electrode experiments and the more recent failures to 
      observe these effects with whole cell patch techniques.
FAU - Schneider, S P
AU  - Schneider SP
AD  - Department of Anatomy and Neuroscience Program, Michigan State University, East 
      Lansing, Michigan 48824, USA.
FAU - Eckert, W A 3rd
AU  - Eckert WA 3rd
FAU - Light, A R
AU  - Light AR
LA  - eng
GR  - DA-04420/DA/NIDA NIH HHS/United States
GR  - NS-16433/NS/NINDS NIH HHS/United States
GR  - NS-25771/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurophysiol
JT  - Journal of neurophysiology
JID - 0375404
RN  - 0 (Narcotics)
RN  - 0 (Potassium Channels)
RN  - 0 (Receptors, Opioid, mu)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/pharmacology
MH  - Animals
MH  - Cricetinae
MH  - Electric Stimulation
MH  - Electrophysiology
MH  - Female
MH  - Guanosine Triphosphate/pharmacology
MH  - Histocytochemistry
MH  - In Vitro Techniques
MH  - Male
MH  - Membrane Potentials/physiology
MH  - Mesocricetus
MH  - Narcotics/*pharmacology
MH  - Neurons/*drug effects
MH  - Patch-Clamp Techniques
MH  - Potassium Channels/drug effects/*physiology
MH  - Rats
MH  - Receptors, Opioid, mu/drug effects
MH  - Substantia Gelatinosa/*cytology/drug effects
EDAT- 1998/12/24 03:02
MHDA- 2001/03/28 10:01
CRDT- 1998/12/24 03:02
PHST- 1998/12/24 03:02 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1998/12/24 03:02 [entrez]
AID - 10.1152/jn.1998.80.6.2954 [doi]
PST - ppublish
SO  - J Neurophysiol. 1998 Dec;80(6):2954-62. doi: 10.1152/jn.1998.80.6.2954.