Enhancement of low-voltage-activated calcium currents by group II metabotropic glutamate receptors in rat retinal ganglion cells.
Current through voltage-gated calcium channels of rat retinal ganglion cells was recorded using the whole-cell patch-clamp technique. All cells displayed high-voltage-activated currents, and 75% of these also displayed low-voltage-activated (LVA) currents. Currents could be separated on the basis of their voltage/time dependence and sensitivity to nickel ions. The group II metabotropic glutamate receptor (mGluR) agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC; 100 microM) increased LVA current by 40% as did the nonselective mGluR agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (tACPD; 100 microM). Neither the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (100 microM) nor 5-hydroxytryptamine (100 microM) enhanced LVA current. In the presence of (S)-alpha-methyl-4-carboxyphenylglycine (100 microM), a group I/II mGluR antagonist, the tACPD-induced enhancement of LVA current was blocked. The voltage dependence of the activation or inactivation kinetics was unchanged in the presence of tACPD. Inclusion in the pipette solution of GDP-beta-S (1 mM) blocked the enhancement of the LVA current by APDC, whereas GTP-gamma-S (0.5 mM) prevented recovery of the enhancement. The tACPD-mediated enhancement of the LVA current was still present in cells pretreated with pertussis or cholera toxins (500 ng x ml(-1)). Genistein (10 microM) prevented the enhancement of the LVA current. These results suggest that LVA current can be enhanced by activation of mGluR2, by a mechanism that is G-protein dependent and may involve a protein tyrosine kinase step.
Robbins
Jon
J
Sensory Function Group, Centre for Neuroscience Research, King's College, London SE1 1UL, UK. jon.robbins@kcl.ac.uk
Reynolds
A Martyn
AM
Treseder
Sarah
S
Davies
Richard
R
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002772:Cholera Toxin / Q000494:pharmacology; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000502:physiology*
C097299:4-aminopyrrolidine-2,4-dicarboxylic acid; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D002772:Cholera Toxin; D011392:Proline; D019833:Genistein; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium