NMDA-evoked [Ca2+]i increase in salamander retinal ganglion cells: modulation by PKA and adrenergic receptors.
Application of NMDA induces a depolarization and increase of intracellular calcium concentration ([Ca2+]i) in retinal ganglion cells, which cause ganglion cell death in models of glaucoma. In the present study, we investigated the pharmacological mechanism of how NMDA-evoked increase in calcium could be modulated in dissociated retinal ganglion cells from tiger salamander. In these neurons, protein kinase A (PKA) up-regulated the NMDA-evoked [Ca2+]i increase. In the presence of 8-bromo-cAMP or forskolin to stimulate PKA, the elevation level of [Ca2+]i induced by NMDA became even higher; in the presence of H-89, a PKA inhibitor, the NMDA-evoked [Ca2+]i increase was attenuated. In addition, applications of adrenergic compounds were also found to influence the NMDA-evoked [Ca2+]i increase. UK-14,304, a selective alpha2 agonist, reduced the elevation level of [Ca2+]i caused by NMDA. In contrast, isoproterenol, a beta agonist, augmented the NMDA-evoked [Ca2+]i increase. These adrenergic regulations were due to direct activation of adrenoceptors, since modulations of both UK-14,304 and isoproterenol on the NMDA-evoked [Ca2+]i increase were abolished by their respective antagonists. Furthermore, adrenergic regulations were mediated through a PKA-related pathway since PKA inhibitor blocked adrenergic regulations. The possible modulatory site(s) by PKA was also discussed.
Han
Yi
Y
Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77030, USA. yhan@softhome.net
Wu
Samuel M
SM
D018663:Adrenergic Agents / Q000494:pharmacology; D000557:Ambystoma; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology*; D009994:Osmolar Concentration; D011941:Receptors, Adrenergic / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism*
D018663:Adrenergic Agents; D018690:Excitatory Amino Acid Agonists; D011941:Receptors, Adrenergic; D016202:N-Methylaspartate; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium