Developmental Regulation of Small-Conductance Ca²⁺-Activated K⁺ Channel Expression and Function in Rat Purkinje Neurons

Abstract

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 potassium channels of the SK type modulate membrane excitability and are important determinants of the firing properties of central neurons. Increases in the intracellular calcium concentration 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 transients. However, the role of SK channels in neuronal development 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 pharmacological tools have revealed for the first time the presence of an afterhyperpolarizing current (I(AHP)) 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 correlated with the expression of I(AHP) 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.

Intermediate conductance calcium-activated potassium channels modulate summation of parallel fiber input in cerebellar Purkinje cells

“…2G). As predicted by a reported decrease in KCa2.2 mRNA through development (27), the KCa2.2 band was detectable but relatively faint compared with KCa1.1 or KCa3.1 (Fig. 2G).…”

Cerebellar ataxia and Purkinje cell dysfunction caused by Ca 2+ -activated K + channel deficiency

“…3c Right). PCs from both WT and BK Ϫ/Ϫ mice showed two distinct spontaneous firing patterns (28,29): tonic-firing PCs vs. repetitive bursting PCs (Fig. 3b) and the proportions of these were not statistically different between BK Ϫ/Ϫ (20.0% tonic, 26.7% bursting) and WT mice (53.3% tonic, 46.7% bursting) (Fig.…”

Dendritic Control of Spontaneous Bursting in Cerebellar Purkinje Cells

“…Both SK and BK channels are present in Purkinje neurons (Jacquin and Gruol, 1999;Cingolani et al, 2002;Edgerton and Reinhart, 2003;Khodakhah, 2002b, 2003) and both contribute to burst firing in dissociated Purkinje cells (Swensen and Bean, 2003). BK channels also contribute to repolarization of dendritic calcium spikes (Edgerton and Reinhart, 2003).…”

“…A striking feature of spontaneously active Purkinje neurons is their tendency to fire in bursts. In dissociated cells (Swensen and Bean, 2003), in cerebellar slices (Cingolani et al, 2002;Womack and Khodakhah, 2002a), and in vivo (Jaeger and Bower, 1994), Purkinje neurons exhibit trains of spontaneous bursts that often arise from their intrinsic membrane properties (Womack and Khodakhah, 2002a;Swensen and Bean, 2003).…”