Transient Activation of GABA(B) Receptors Suppresses SK Channel Currents in Substantia Nigra Pars Compacta Dopaminergic Neurons

Dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) are richly innervated by GABAergic neurons. The postsynaptic effects of GABA on SNc DA neurons are mediated by a mixture of GABA(A) and GABA(B) receptors. Although activation of GABA(A) receptors inhibits spike generation, the consequences of GABA(B) receptor activation are less well characterized. To help fill this gap, perforated patch recordings were made from young adult mouse SNc DA neurons. Sustained stimulation of GABA(B) receptors hyperpolarized SNc DA neurons, as previously described. However, transient stimulation of GABA(B) receptors by optical uncaging of GABA did not; rather, it reduced the opening of small-conductance, calcium-activated K(+) (SK) channels and increased the irregularity of spiking. This modulation was attributable to inhibition of adenylyl cyclase and protein kinase A. Thus, because suppression of SK channel activity increases the probability of burst spiking, transient co-activation of GABA(A) and GABA(B) receptors could promote a pause-burst pattern of spiking.