GABAergic activation of an inwardly rectifying K⁺ current in mouse cerebellar Purkinje cells

Cerebellar Purkinje cells integrate motor information conveyed by excitatory synaptic inputs from parallel and climbing fibres. Purkinje cells abundantly express B-type G-protein-coupled γ-aminobutyric acid receptors (GABA_BR) that are assumed to mediate major responses, including postsynaptic modulation of the synaptic inputs. However, the identity and function of effectors operated by GABA_BR are not fully elucidated. Here we characterized an inwardly rectifying current activated by baclofen (I_bacl), a GABA_BR agonist, in cultured mouse Purkinje cells using a ruptured-patch whole-cell technique. I_bacl is operated by GABA_BR via G_i/o-Proteins, as it is not inducible in pertussis-toxin-pretreated cells. I_bacl is carried by K⁺ because its reversal potential shifts with the equilibrium potential of K⁺. I_bacl is blocked by 10^-3 M Ba²⁺ or Cs⁺, and 10^-8 M tertiapin-Q. Upon the onset and offset of a hyperpolarizing step, I_bacl is activated and deactivated, respectively, with double-exponential time courses (time constants, < 1 ms and 30-80 ms). Based on similarities in the above properties, G-protein-coupled inwardly rectifying K⁺ (GIRK) channels are thought to be responsible for I_bacl. Perforated-patch recordings from cultured Purkinje cells demonstrate that I_bacl hyperpolarizes the resting potential and the peak level achieved by glutamate-evoked potentials initiated in the dendrites. Moreover, cell-attached recordings from Purkinje cells in cerebellar slices demonstrate that I_bacl impedes spontaneous firing. Therefore, I_bacl may reduce the postsynaptic and intrinsic excitability of Purkinje cells under physiological conditions. These findings give a new insight into the role of GABA_BR signalling in cerebellar information processing.