Characterization of the inward current induced by metabotropic glutamate receptor stimulation in rat ventromedial hypothalamic neurones

J Physiol. 1997 Nov 1;504 ( Pt 3)(Pt 3):649-63. doi: 10.1111/j.1469-7793.1997.649bd.x.

Abstract

1. Whole-cell patch clamp recordings were made from rat ventromedial hypothalamic neurones in slices of brain tissue in vitro. Bath application of 50 microM (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) depolarized all neurones tested by activation of an inward current of approximately 55 pA at -60 mV. 2. The inward current elicited by 1S,3R-ACPD was unaffected by K+ channel blockade with external Cs+, Ba2+ or TEA. However, the current was significantly reduced by replacement of the external NaCl with either Tris-HCl or LiCl. 3. The 1S,3R-ACPD-induced current was reduced by the heavy metal ions Ni2+ or La3+ and also by the Na(+)-Ca2+ exchange current inhibitor 3',4'-dichlorobenzamil. 4. The effects of 1S,3R-ACPD were mimicked by the group I metabotropic agonist 3,5-dihydroxyphenylglycine (DHPG) but not by the group III selective agonist, L-2-amino-4-phosphonobutanoate (L-AP4). Furthermore, the effects of 1S,3R-ACPD were inhibited by the metabotropic antagonists alpha-methyl-4-carboxyphenylglycine (MCPG) and 1-aminoindan-1,5-dicarboxylic acid (AIDA) but not by the presynaptic metabotropic receptor antagonists alpha-methyl-4-phosphonophenylglycine (MPPG) or alpha-methyl-4-tetrazolylphenylglycine (MTPG). 5. Photorelease of caged GDP beta S inside neurones irreversibly blocked the 1S,3R-ACPD-induced current whilst photolysis of caged GTP gamma S inside neurones irreversibly potentiated this current. 6. The PLC inhibitor U-73,122 significantly reduced the size of the inward current induced by 1S,3R-ACPD. This effect was not mimicked by the inactive analogue U-73,343. 7. Flash photolysis of the caged calcium chelator diazo-2 inside neurones diminished the response to 1S,3R-ACPD. 8. It is concluded that group I metabotropic glutamate receptors depolarize neurones in the VMH by activation of a Na(+)-Ca2+ exchange current through a G-protein coupled increase in intracellular Ca2+.

MeSH terms

  • Animals
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cycloleucine / analogs & derivatives
  • Cycloleucine / pharmacology
  • Electric Stimulation
  • Electrophysiology
  • In Vitro Techniques
  • Ion Channels / drug effects
  • Ion Channels / metabolism
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • Photolysis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / drug effects
  • Receptors, Metabotropic Glutamate / metabolism*
  • Sodium / physiology
  • Type C Phospholipases / antagonists & inhibitors
  • Ventromedial Hypothalamic Nucleus / cytology
  • Ventromedial Hypothalamic Nucleus / drug effects
  • Ventromedial Hypothalamic Nucleus / metabolism*

Substances

  • Ion Channels
  • Receptors, Metabotropic Glutamate
  • Cycloleucine
  • 1-amino-1,3-dicarboxycyclopentane
  • Sodium
  • Type C Phospholipases