Does ethanol activate G-protein coupled inwardly rectifying K+channels?

G-protein coupled inwardly rectifying K+ (GIRK) channels have been reported to be targets of ethanol actions. We investigated if ethanol affects native GIRK channels in rat brain tissues at clinically relevant concentrations using brain slices containing the ventrolateral periaqueductal gray (PAG), an area related to pain regulation. Ethanol did not affect the membrane current elicited by hyperpolarization ramps at concentrations up to 150 mM. However, at 200–300 mM, which is above the lethal level, it activated a barium-sensitive GIRK current in 30–57% of neurons. In neurons unresponsive to ethanol, baclofen, the mu-opioid or nociceptin successfully activated GIRK channels. It is suggested that GIRK channels of the ventrolateral PAG are unlikely to be targets of the analgesic action of ethanol.

[1]  L. Chiou,et al.  ATP-sensitive K+ channels and cellular actions of morphine in periaqueductal gray slices of neonatal and adult rats. , 2001, The Journal of pharmacology and experimental therapeutics.

[2]  M. Stoffel,et al.  Potassium channels as targets for ethanol: studies of G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2) null mutant mice. , 2001, The Journal of pharmacology and experimental therapeutics.

[3]  L. Chiou.  Differential antagonism by naloxone benzoylhydrazone of the activation of inward rectifying K+ channels by nociceptin and a µ-opioid in rat periaqueductal grey slices , 2001, Naunyn-Schmiedeberg's Archives of Pharmacology.

[4]  K Genz,et al.  Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. , 2000, Science.

[5]  H. Niki,et al.  Ethanol opens G-protein-activated inwardly rectifying K+ channels , 1999, Nature Neuroscience.

[6]  R. Harris,et al.  G-protein-coupled inwardly rectifying potassium channels are targets of alcohol action , 1999, Nature Neuroscience.

[7]  L. Chiou.  [Phe1ψ(CH2‐NH)Gly2]nociceptin‐(1–13)‐NH2 activation of an inward rectifier as a partial agonist of ORL1 receptors in rat periaqueductal gray , 1999, British journal of pharmacology.

[8]  L. Chiou,et al.  Mechanism underlying increased neuronal activity in the rat ventrolateral periaqueductal grey by a μ‐opioid , 1999, The Journal of physiology.

[9]  N. Akaike,et al.  μ-opioid agonist-induced activation of G-protein-coupled inwardly rectifying potassium current in rat periaqueductal gray neurons , 1999, Neuroscience.

[10]  M. Christie,et al.  Actions of the ORL1 Receptor Ligand Nociceptin on Membrane Properties of Rat Periaqueductal Gray Neurons In Vitro , 1997, The Journal of Neuroscience.

[11]  Y. Jan,et al.  Heteromultimerization of G-Protein-Gated Inwardly Rectifying K+ Channel Proteins GIRK1 and GIRK2 and Their Altered Expression in weaver Brain , 1996, The Journal of Neuroscience.

[12]  W. Stühmer,et al.  IRK(1–3) and GIRK(1–4) Inwardly Rectifying K+Channel mRNAs Are Differentially Expressed in the Adult Rat Brain , 1996, The Journal of Neuroscience.

[13]  S. A. Shefner,et al.  Ethanol enhances inward rectification in rat locus ceruleus neurons by increasing the extracellular potassium concentration. , 1994, The Journal of pharmacology and experimental therapeutics.

[14]  B. Chieng,et al.  Inhibition by opioids acting on μ‐receptors of GABAergic and glutamatergic postsynaptic potentials in single rat periaqueductal gray neurones in vitro , 1994, British journal of pharmacology.

[15]  A I Basbaum,et al.  Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. , 1984, Annual review of neuroscience.

[16]  H. Pitkow,et al.  Basic and Clinical Pharmacology , 1983 .

[17]  L. A. Greenberg,et al.  STUDIES ON THE ABSORPTION, DISTRIBUTION AND ELIMINATION OF ALCOHOL VI. THE PRINCIPLES GOVERNING THE CONCENTRATION OF ALCOHOL IN THE BLOOD AND THE CONCENTRATION CAUSING RESPIRATORY FAILURE , 1940 .