Developmental regulation of small-conductance Ca2+-activated K+ channel expression and function in rat Purkinje neurons

Calcium transients play an important role in the early and later phases of differentiation and maturation of single neurons and neuronal networks. Small-conductance calcium-activated po- tassium channels of the SK type modulate membrane excitabil- ity and are important determinants of the firing properties of central neurons. Increases in the intracellular calcium concen- tration activate SK channels, leading to a hyperpolarization of the membrane potential, which in turn reduces the calcium inflow into the cell. This feedback mechanism is ideally suited to regulate the spatiotemporal occurrence of calcium tran- sients. However, the role of SK channels in neuronal develop- ment has not been addressed so far. We have concentrated on the ontogenesis and function of SK channels in the developing rat cerebellum, focusing particularly on Purkinje neurons. Electrophysiological recordings combined with specific phar- macological tools have revealed for the first time the presence of an afterhyperpolarizing current (IAHP ) in immature Purkinje cells in rat cerebellar slices. The channel subunits underlying this current were identified as SK2 and localized by in situ hybridization and subunit-specific antibodies. Their expression level was shown to be high at birth and subsequently to decline during the first 3 weeks of postnatal life, both at the mRNA and protein levels. This developmental regulation was tightly corre- lated with the expression of IAHP and the prominent role of SK2 channels in shaping the spontaneous firing pattern in young, but not in adult, Purkinje neurons. These results provide the first evidence of the developmental regulation and function of SK channels in central neurons.