@entity1943 receptor subtype 4 modulates L-type XXXX channels via Gby and @entity6164 signaling in rat @entity2479 cells.

@entity2479 @entity19 @entity63793 @entity11009 @entity460 @entity6164 @entity141 @entity1943
Abstract @entity1943 subtype-4 receptors ( @entity63793 ) inhibit L-type @entity460 channel currents (ICa) in @entity2479 cells (RGCs). Here we identify the signaling pathways involved in @entity63793 stimulation leading to suppression of ICa in RGCs. Whole cell patch clamp recordings were made on isolated immunopanned RGCs using barium as a charge carrier to isolate ICa. Application of the selective @entity63793 agonist, L-803 (10  nM), reduced ICa by @entity19 %. Pretreatment of cells with pertussis toxin (Gi/o inhibitor) did not prevent the action of L-803, which reduced ICa by 34.7%. To determine the involvement of Gby subunits after @entity63793 activation, depolarizing pre-pulse facilitation paradigms were used to remove voltage-dependent inhibition of @entity460 channels. Pre-pulse facilitation did not reverse the inhibitory effects of L-803 on ICa (8.4  vs. 8.8% reductions, ctrl vs. L-803); however, pharmacologic inhibition of Gby reduced ICa suppression by L-803 (23.0%, p<0.05). Inhibition of @entity6164 ( @entity11009 ; GFX) showed a concentration-dependent effect in preventing the action of L-803 on ICa (1   M GFX, 34.3%; 5   M GFX, 14.6%, p<0.05). When both @entity6164 and Gby were inhibited, the effects of L-803 on ICa were blocked (1.8%, p<0.05). These results suggest that @entity63793 stimulation modulates RGC @entity460 channels via Gby and @entity6164 activation. Since reducing intracellular @entity141 is known to be neuroprotective in RGCs, modulating these @entity63793 signaling pathways may provide insights to the discovery of unique therapeutic targets to reduce intracellular @entity141 levels in RGCs.
