The effect of SK channel modulators on the simple spike firing frequency in discharge of cerebellar Purkinje cells in laboratory mice

The activity of cerebellar Purkinje cells is studied as affected by CyPPA, a positive modulator of small-conductance calcium-activated potassium channels type 3 and 2 (SK3/SK2), and NS309, an activator of small- and intermediate-conductance calcium-activated potassium channels (IK/SK), in male two-month-old laboratory mice. CyPPA decreases the simple spike firing frequency in the discharge of Purkinje cells by an average of 25% 1 hour after application of 1mM of the compound. An application of 100 μM of NS309 reduces the simple spike firing frequency by an average of 47% during the same period. These results confirm the hypothesis that SK channels may be involved in the downregulation of simple spike firing frequency in Purkinje cells. The frequency-regulating effect of NS309 is stronger, suggesting that IK/SK channels play a decisive role in the regulation of Purkinje cell spiking activity. Since an increase of simple spike firing frequency in these cells is symptomatic of many locomotor activity disorders, e.g., spinocerebellar ataxia, the substances studied or their functional analogues might be of medicinal interest.