The mGlu1 antagonist CPCCOEt enhances the climbing fibre response in Purkinje neurones independently of glutamate receptors.
CPCCOEt (7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester) is frequently used to test for the involvement of mGlu1 receptors. Using whole-cell voltage recording from Purkinje cells in slices of rat cerebellum we find that CPCCOEt, at concentrations used to block mGlu1 receptors, causes an enhancement of the climbing fibre response. Application of alternative antagonists with activity at mGlu1 neither mimicked nor occluded the effects of CPCCOEt. Receptor antagonists demonstrated that this non-mGlu1 action of CPCCOEt was not mediated by other mGlu receptors or GABA(B) receptors. Voltage-clamped climbing fibre EPSCs are unaffected by CPCCOEt whilst application of a glutamate transport blocker did not occlude the CPCCOEt effect. This suggests that a postsynaptic voltage-dependent component of the complex climbing fibre response is the target. We have found no evidence for the involvement of the hyperpolarisation-activated current, I(h), and calcium-activated conductances. Voltage-gated sodium, calcium and potassium channels are possible targets with inhibition of a potassium channel the most likely. Awareness of this non-mGlu-mediated effect of CPCCOEt is likely to be important for the correct interpretation of its actions.
Fukunaga
Izumi
I
Departments of Physiology and Anatomy, University College London, Gower Street, London WC1E 6BT, UK.
Yeo
Christopher H
CH
Batchelor
Andrew M
AM
D000818:Animals; D000831:Animals, Newborn; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology; D002531:Cerebellum / Q000166:cytology; D002867:Chromones / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D009412:Nerve Fibers / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000502:physiology*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats
C117789:7-(hydroxyimino)cyclopropan(b)chromen-1a-carbxoylic acid ethyl ester; D001565:Benzoates; D002867:Chromones; D018691:Excitatory Amino Acid Antagonists; D011743:Pyrimidines; C082246:ICI D2788; C079694:alpha-methyl-4-carboxyphenylglycine; D005998:Glycine