Figure 6.
Baclofen inhibits a postsynaptic K+ conductance in CA1 pyramidal cells of GABAB(2)-/- mice. A, Holding current (at -50 mV) plotted versus time for wild-type (top, filled circles) and GABAB(2)-/- (bottom, open circles) mice. Whereas both baclofen (50 μm) and adenosine (100 μm) induce an outward current in wild-type mice, baclofen induces an inward current in GABAB(2)-/- mice. Baclofen-induced effects were blocked by application of the GABAB receptor antagonist CGP55845A (2 μm) in wild-type as well as in GABAB(2)-/- mice. B, Summary graph illustrating the baclofen-induced inward current at -50 mV in GABAB(2)-/- mice. Baclofen-induced currents: wild-type, n = 5; GABAB(2)-/-, n = 9. Adenosine-induced currents: wild-type, n = 5; GABAB(2)-/-, n = 4. C, Current-voltage relationship of the baclofen-induced conductance in wild-type (black trace) and GABAB(2)-/- (gray trace) mice. Currents were obtained by calculating the difference between the I-V curves before and after addition of baclofen. Whereas a current with a positive slope conductance is induced by baclofen in wild-type mice, a current with negative slope conductance is induced in GABAB(2)-/- mice. D, Current-voltage relationship of the adenosine-induced conductance in wild-type mice (black trace) is not different from GABAB(2)-/- mice (gray trace). E, Baclofen induces the closure of K+ channels in GABAB(2)-/- mice. Raising extracellular [K+] concentration shifts the reversal potential of the baclofen-induced current. F, The baclofen-induced conductance change is mediated by G-protein activation. In the presence of intracellular GDPβS (1 mm for 25 min), both the baclofen-induced (control, n = 5; GDPβS, n = 5) and adenosine-induced (control, n = 4; GDPβS, n = 5) currents are inhibited in GABAB(2)-/- mice. G, Changes in the holding current (at -50 mV) in response to baclofen (Bacl.) after preincubation with adenosine. H, Summary graph illustrating that the effects of adenosine and baclofen are not fully additive. In wild-type neurons (+/+), the effect of a combined application of adenosine and baclofen is lower than the sum of the individual effects [Adenosine + Bacl. (calculated)]. In GABAB(2)-/- (-/-) neurons, the effects of adenosine and baclofen are not fully additive. Application of baclofen does not obliterate the adenosine response. I, Left, Summary graph illustrating postsynaptic conductance changes induced by baclofen in wild-type (n = 5), GABAB(2)+/- (n = 10), and GABAB(1)-/- (n = 4) mice. The conductance changes were blocked by application of the GABAB(1) receptor antagonist CGP55845A (2 μm; wild-type, n = 4; GABAB(2)-/-, n = 8). Adenosine-induced conductance changes are not different between genotypes (wild-type, n = 4; GABAB(2)-/-, n = 4; GABAB(1)-/-, n = 3). *p < 0.05; **p < 0.01.