Excitability control by a GABA_B receptor-operated inwardly rectifying K⁺ current in cerebellar Purkinje cells

Abstract

Cerebellar Purkinje cells highly express B-type G-protein-coupled γ-aminobutyric acid receptors (GABA_BR). However, the functional contribution of GABA_BR is not fully elucidated in this cell type. Here we identified a GABA_BR agonist (baclofen)-induced inwardly rectifying current (I_bacl) in cultured mouse Purkinje cells, using a ruptured-patch whole-cell technique. I_bacl is coupled to GABA_BR via G_i/o-proteins as it is not inducible in pertussis toxin-treated cells. I_bacl is carried by K⁺ but not Na⁺. I_bacl is blocked by Ba²⁺, Cs⁺, and tertiapin-Q. I_bacl is activated rapidly upon hyperpolarization with a double-exponential time-course (time constants, 0.8 and 80 ms). These results indicate that I_bacl is mediated by G-protein-coupled inwardly rectifying K⁺ channels. Perforated-patch recordings demonstrate that I_bacl hyperpolarizes the resting potential and the peak level of glutamate-evoked potentials initiated in the dendrites. Moreover, cell-attached recordings in cerebellar slices demonstrate that I_bacl slows down the rate of spontaneous firing. I_bacl activation via GABA_BR reduces the postsynaptic and intrinsic excitability of Purkinjes and may thereby influence the integration of motor information conveyed by excitatory parallel and climbing fibers. [Jpn J Physiol 55 Suppl:S150 (2005)]