Figure 7.

IP₃-evoked membrane hyperpolarizations are strongly suppressed by dantrolene. A, Traces show changes in membrane potential in representative neurons from NonTg (left) and 3xTg-AD mice (right) after photolysis flashes of 100 ms duration in control conditions (top) and after adding 10 μm dantrolene (bottom). B, Relationships between photolysis flash duration and magnitude of the IP₃-evoked hyperpolarization. The main graph shows data from NonTg (n = 17; black squares) and Tg (n = 31; gray circles) neurons before (filled symbols) and during (open symbols) dantrolene application. The inset shows mean data comparing effects of ryanodine in Tg neurons (n = 16; closed circles) with dantrolene in Tg neurons (open squares; same data as in the main graph). C, IP₃-mediated reduction in spiking frequency is suppressed by dantrolene. The top trace shows spikes evoked by periodic injections of depolarizing current. A photolysis flash (100 ms) was delivered at the arrow to photorelease IP₃, resulting in a reduced spiking frequency for several seconds. The bottom trace was obtained using the same protocol in the same neuron while continually superfusing dantrolene (10 μm). Error bars represent SEM.