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 B R) that are assumed to mediate major responses, including postsynaptic modulation of the synaptic inputs. However, the identity and function of effectors operated by GABA B R are not fully elucidated. Here we characterized an inwardly rectifying current activated by baclofen ( I bacl ), a GABA B R agonist, in cultured mouse Purkinje cells using a ruptured‐patch whole‐cell technique. I bacl is operated by GABA B R 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 Ba 2+ 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 B R signalling in cerebellar information processing.