Figure 7.
Manipulation of intracellular cGMP levels modulates the membrane activity of striatal neurons. Striatal neurons were recorded after intracellular application (∼5 min) of either vehicle (0.5% DMSO), the GC inhibitor ODQ (100 μm), ODQ plus cGMP (1 mm), or the PDE inhibitor zaprinast (200 μm). A, Left, After vehicle injection, striatal neurons (n = 6) exhibited typical rapid spontaneous shifts in steady-state membrane potential and irregular spontaneous spike discharge. Right, Time interval plots of membrane potential activity recorded from control neurons demonstrated bimodal membrane potential distributions indicative of bistable membrane activity. B, Left, Striatal neurons recorded after ODQ injection (n = 5) exhibited significantly lower amplitude up events compared with vehicle-injected controls and rarely fired action potentials. Right, The depolarized portion of the membrane potential distribution of neurons recorded after ODQ injection was typically shifted leftward (hyperpolarized) compared with controls. C, Left, Striatal neurons recorded after ODQ and cGMP injection rarely fired action potentials but exhibited high amplitude up events with extraordinarily long durations. Right, The membrane potential distribution of neurons recorded after ODQ and cGMP injection was similar to controls, indicating that cGMP partially reversed some of the effects of ODQ. D, Left, Striatal neurons recorded after intracellular injection of zaprinast (n = 5) exhibited high amplitude up events with extraordinarily long durations. Additionally, all of the cells fired action potentials at relatively high rates (0.4-2.2 Hz). Right, The membrane potential distribution of these neurons was typically shifted rightward (depolarized) compared with controls. Arrows indicate the membrane potential at its maximal depolarized and hyperpolarized levels. E, Left, The mean ± SEM up-state amplitude was reduced after intracellular injection of ODQ (n = 5; *p < 0.05; ANOVA with Dunnett's post hoc test). Right, The mean ± SEM up-state duration was significantly prolonged during cGMP/ODQ and zaprinast injections (n = 5; *p < 0.05; ANOVA with Dunnett's post hoc test).