The toxin helothermine affects potassium currents in newborn rat cerebellar granule cells

Helothermine, a recently isolated toxin from the venom of the Mexican beaded lizard Heloderma horridum horridum was tested on K currents of newborn rat cerebellar granule cells. In whole-cell voltageclamp experiments, cerebellar granule neurons exhibited at least two different K current components: a first transient component which is similar to an I-type current, is characterized by fast activating and inactivating kinetics and blocked by 4-aminopyridine; a second component which is characterized by noninactivating kinetics, is blocked by tetraetylammonium ions and resembles the classical delayed-rectifier current. When added to the standard external solution at concentrations ranging between 0.1 and 2 ?m helothermine reduced the pharmacologically isolated I-type current component in a voltage- and dose-dependent way, with a half-maximal inhibitory concentration (IC) of 0.52 ?m. A comparison between control and nelothermine-modified peak transient currents shows a slowdown of activation and inactivation kinetics. The delayed-rectifier component inhibition was concentration dependent (IC = 0.86 ?m) but not voltage dependent. No frequency-or use-dependent block was observed on both K current types. Perfusing the cells with control solution resulted in quite a complete current recovery. We conclude that helothermine acts with different affinities on two types of K current present in central nervous system neurons. © 1994 Springer-Verlag New York Inc.