Multiple second-messenger system modulation of voltage-activated calcium currents in teleost retinal horizontal cells.
Two voltage-activated calcium currents, a transient T-type and a PL-sustained type, have been measured in isolated, cultured white bass horizontal cells. These two voltage-activated calcium currents were found to be modulated by two independent second-messenger systems. Furthermore, activation of either second-messenger system led to similar changes in calcium current activity. Activation of the cyclic AMP second-messenger pathway or the sn-1,2-diacylglycerol (DAG) second-messenger system resulted in a significant decrease in the amplitude of the transient current and a simultaneous large increase in the amplitude of the sustained current. Both second-messenger systems achieved their effects through protein phosphorylation. The cyclic AMP pathway resulted in the activation of protein kinase A (PKA) and the DAG pathway worked to activate protein kinase C (PKC). Two protein kinase inhibitors were analyzed in this study for their ability to inhibit second-messenger activated protein kinase activity and separate the two pathways. The peptide cyclic AMP-dependent protein kinase inhibitor and staurosporine were found to be nonspecific at high concentrations and inhibited both second-messenger pathways. At low concentrations however, staurosporine specifically inhibited only PKC, whereas adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase inhibitor was selective for PKA. Both second-messenger systems were activated by the neuromodulator, dopamine. Thus one agonist can initiate multiple second-messenger systems leading to similar changes in voltage-activated calcium current activity. The modulatory action on calcium currents produced by one second-messenger system added to the modulatory action resulting from activation of the other second-messenger system. The effect is to alter the magnitude of the horizontal cell calcium currents.
Pfeiffer-Linn
C L
CL
John Moran Eye Center, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.
Lasater
E M
EM
D000818:Animals; D001492:Bass; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D009474:Neurons / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000502:physiology*; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D015220:Calcium Channels; D004075:Diglycerides; C053907:8-cyclopentyl-1,3-dimethylxanthine; D013806:Theophylline; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D004298:Dopamine