PROTEIN-KINASES MODULATE 2 GLYCINE CURRENTS IN SALAMANDER RETINAL GANGLION-CELLS

1. Protein kinase modulation of glycine-activated currents was examine d in acutely dissociated ganglion cells from tiger salamander retina u sing whole-cell voltage-clamp techniques. 2. Glycine (100 mu M) induce d an outward chloride current in cells clamped at 0 mV. Go-application of 50 mu M forskolin made the glycine-induced current more transient. The combination of forskolin and glycine reduced the later portion of current response without changing the initial peak amplitude. 3. 3-Is obutyl-1-methylxanthine (IBMX) or 8-bromoadenosine 3',5'-cyclic monoph osphate (8-Br-cAMP) produced effects similar to those of forskolin. H- 89, a protein kinase A (PKA) inhibitor, blocked the effect of forskoli n. 4. A protein kinase C (PKC) activator, OAG (1-oleoyl-2-acetyl-sn-gl ycerol), also made the glycine response more transient. Unlike PRA ana logues, OAG enhanced the glycine peak response without changing the gl ycine late response. OAG effects were blocked by 1 mu M GF-109203X, a PKC inhibitor. 5. Nanomolar concentrations of strychnine selectively b locked the fast phase of the glycine current and reversed the effect o f GAG, but not that of forskolin. Conversely, forskolin occluded the e ffect of 5,7-dichlorokynurenic acid, which selectively suppresses the late phase of the glycine current. The action of OAG was not blocked b y 5,7-dichlorokynurenic acid. 6. Thus, through a differential modulati on, both protein kinase A and C shorten the decay time of the glycine current. PKA suppresses the Slow component, while PKC potentiates the fast component.