PMID- 17329078
OWN - NLM
STAT- MEDLINE
DCOM- 20070806
LR  - 20131121
IS  - 0887-2333 (Print)
IS  - 0887-2333 (Linking)
VI  - 21
IP  - 4
DP  - 2007 Jun
TI  - Inhibition by cocaine of G protein-activated inwardly rectifying K+ channels 
      expressed in Xenopus oocytes.
PG  - 656-64
AB  - Cocaine, a commonly abused psychostimulant, interacts with not only transporters 
      for dopamine, serotonin and norepinephrine but also several receptors and 
      channels. However, the molecular mechanisms underlying the various effects of 
      cocaine remain to be clarified. Using the Xenopus oocyte expression assay, we 
      investigated the effects of cocaine on G protein-activated inwardly rectifying K+ 
      (GIRK) channels, which regulate neuronal excitability and the heart rate. In 
      oocytes injected with mRNAs for GIRK1/GIRK2, GIRK2 or GIRK1/GIRK4 subunits, 
      cocaine reversibly reduced basal GIRK inward currents. The inhibition by cocaine 
      at the toxic levels was concentration-dependent, but voltage-independent and 
      time-independent during each voltage pulse. However, methylphenidate, 
      methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) at their toxic 
      concentrations had little effect on the channels. Additionally, Kir1.1 and Kir2.1 
      channels were insensitive to all of the drugs. The inhibition by cocaine, which 
      exists mainly in a protonated form at pH 7.4, was not affected by extracellular 
      pH 9, at which the proportion of the uncharged form increases, suggesting the 
      inhibition by both forms with similar effectiveness, and at physiological pH the 
      effect being predominantly due to the protonated cocaine. Our results suggest 
      that inhibition of GIRK channels by cocaine may contribute to some of its toxic 
      effects.
FAU - Kobayashi, Toru
AU  - Kobayashi T
AD  - Division of Psychobiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, 
      Setagaya-ku, Tokyo 156-8585, Japan. torukoba@bri.niigata-u.ac.jp
FAU - Nishizawa, Daisuke
AU  - Nishizawa D
FAU - Iwamura, Tatsunori
AU  - Iwamura T
FAU - Ikeda, Kazutaka
AU  - Ikeda K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070120
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (G Protein-Coupled Inwardly-Rectifying Potassium Channels)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (RNA, Messenger)
RN  - 207ZZ9QZ49 (Methylphenidate)
RN  - 44RAL3456C (Methamphetamine)
RN  - I5Y540LHVR (Cocaine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Brain Chemistry/drug effects
MH  - Central Nervous System Stimulants/pharmacology
MH  - Cocaine/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Electrophysiology
MH  - Female
MH  - G Protein-Coupled Inwardly-Rectifying Potassium Channels/*antagonists & 
      inhibitors/genetics
MH  - Heart/drug effects
MH  - Methamphetamine/pharmacology
MH  - Methylphenidate/pharmacology
MH  - Mice
MH  - Myocardium/metabolism
MH  - N-Methyl-3,4-methylenedioxyamphetamine/pharmacology
MH  - Plasmids/genetics
MH  - *Potassium Channel Blockers
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Xenopus laevis
EDAT- 2007/03/03 09:00
MHDA- 2007/08/07 09:00
CRDT- 2007/03/03 09:00
PHST- 2006/08/03 00:00 [received]
PHST- 2006/12/13 00:00 [revised]
PHST- 2007/01/05 00:00 [accepted]
PHST- 2007/03/03 09:00 [pubmed]
PHST- 2007/08/07 09:00 [medline]
PHST- 2007/03/03 09:00 [entrez]
AID - S0887-2333(07)00020-3 [pii]
AID - 10.1016/j.tiv.2007.01.009 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2007 Jun;21(4):656-64. doi: 10.1016/j.tiv.2007.01.009. Epub 
      2007 Jan 20.