Effects of Src tyrosine kinase inhibitor and MEK inhibitors on the DHPG-induced inward current in MLIs.

<p>(A) Representative traces under control conditions and in the presence of the Src tyrosine kinase inhibitor PP2 (30 µM) and the inactive PP2 analog PP3 (10 µM) are shown. Average traces were obtained from three continuous current events. (B) Time courses of the effects of PP2 and PP3 on the DHPG-induced inward current. The DHPG-current was suppressed by PP2 (black circles, <i>n</i> = 5) but not by PP3 (white circles, <i>n</i> = 4). A black bar indicates the time period of drug application. (C) The G protein-independent component of the DHPG-induced inward current was blocked by the Src tyrosine kinase inhibitor PP2 (30 µM). The DHPG-induced currents were recorded by whole-cell recordings with patch pipettes containing 1 mM GDPβS. The gray line indicates the average percent value during 12–16 min (63%). (D) MEK inhibitors PD98059 (10 µM) and SL327 (10 µM) reduced the DHPG-induced inward current. Averaged traces obtained from three continuous current events are shown. (E) Time courses of the effects of PD98059 (black circles, 10 µM, <i>n</i> = 5) and SL327 (gray circles, 10 µM, <i>n</i> = 4) on the DHPG-induced inward current (<i>n</i> = 5). A black bar indicates the time point for application of the drugs. (F) Schematic diagram of signaling pathways required for the induction of mGluR1-mediated inward current in MLIs. The activation of mGluR1 opens TRPC1 channels through both G protein-dependent and G-protein-independent Src–ERK1/2 signaling pathways. DAG, diacylglycerol.