Forskolin blocks the transient K current of rat cerebellar granule neurons

The action of forskolin (FSK) on voltage-activated K currents was investigated in cerebellar granule cells. FSK reversibly inhibited both A-type (IA) and non-inactivating K currents. IA blockade was more precisely characterized. This effect of FSK was shown to be voltage- and concentration-dependent with an IC50 of 19 microM at +50 mV. 1,9-Dideoxyforskolin (1,9-ddxFSK), a derivative of FSK that does not activate adenylate cyclase, specifically blocked IA, while cAMP-increasing agents had no direct effect on the K currents. The possibility that the non-cAMP mediated effect of FSK occurs through a channel-blocking mechanism and its eventual implications for neuronal excitability are discussed.