Activation of mGluR5 modulates Ca2+ currents in retinal amacrine cells from the chick.
In the inner plexiform layer, amacrine cells receive glutamatergic input from bipolar cells. Glutamate can depolarize amacrine cells by activation of ionotropic glutamate receptors or mediate potentially more diverse changes via activation of G protein-coupled metabotropic glutamate receptors (mGluR5). Here, we asked whether selective activation of metabotropic glutamate receptor 5 is linked to modulation of the voltage-gated Ca2+ channels expressed by cultured GABAergic amacrine cells. To address this, we performed whole-cell voltage clamp experiments, primarily in the perforated-patch configuration. We found that agonists selective for mGluR5, including (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), enhanced the amplitude of the voltage-dependent Ca2+ current. The voltage-dependent Ca2+ current and CHPG-dependent current enhancement were blocked by nifedipine, indicating that L-type Ca2+ channels, specifically, were being modulated. We have previously shown that activation of mGluR5 produces Ca2+ elevations in cultured amacrine cells (Sosa et al., 2002). Loading the cells with 5 mM BAPTA inhibited the mGluR5-dependent enhancement, suggesting that the cytosolic Ca2+ elevations are required for modulation of the current. Although activation of mGluR5 is typically linked to activation of protein kinase C, we found that direct activation of this kinase leads to inhibition of the Ca2+ current, indicating that stimulation of this enzyme is not responsible for the mGluR5-dependent enhancement. Interestingly, direct stimulation of protein kinase A produced an enhancement of the Ca2+ current similar to that observed with activation of mGluR5. Thus, activation of mGluR5 may modulate the L-type voltage-gated Ca2+ current in these GABAergic amacrine cells via activation of protein kinase A, possibly via direct activation of a Ca2(+)-dependent adenylate cyclase.
Sosa
Romina
R
Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.
Gleason
Evanna
E
D025042:Amacrine Cells / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D004553:Electric Conductivity; D004789:Enzyme Activation / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D011493:Protein Kinase C; D002118:Calcium