Enhancement of low-voltage-activated calcium currents by group II metabotropic glutamate receptors in rat retinal ganglion cells

TY - JOUR

T1 - Enhancement of low-voltage-activated calcium currents by group II metabotropic glutamate receptors in rat retinal ganglion cells

AU - Robbins, J

AU - Reynolds, A M

AU - Treseder, S

AU - Davies, R

PY - 2003/7/1

Y1 - 2003/7/1

N2 - 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 11 metabotropic glutamate receptor (mGluR) agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC; 100 muM) increased LVA current by 40% as did the nonselective mGluR agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (tACPD; 100 muM). Neither the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (100 muM) nor 5-hydroxytryptamine (100 muM) enhanced LVA current. In the presence of (S)-alpha-methyl-4-carboxyphenylglycine (100 muM), 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 ml(-1)). Genistein (10 muM) 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. (C) 2003 Elsevier Science (USA). All rights reserved.

AB - 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 11 metabotropic glutamate receptor (mGluR) agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC; 100 muM) increased LVA current by 40% as did the nonselective mGluR agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (tACPD; 100 muM). Neither the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (100 muM) nor 5-hydroxytryptamine (100 muM) enhanced LVA current. In the presence of (S)-alpha-methyl-4-carboxyphenylglycine (100 muM), 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 ml(-1)). Genistein (10 muM) 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. (C) 2003 Elsevier Science (USA). All rights reserved.

UR - http://www.scopus.com/inward/record.url?scp=0037678516&partnerID=8YFLogxK

U2 - 10.1016/S1044-7431(03)00056-3

DO - 10.1016/S1044-7431(03)00056-3

M3 - Article

VL - 23

SP - 341

EP - 350

JO - Molecular and Cellular Neurosciences

JF - Molecular and Cellular Neurosciences

IS - 3

ER -