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 voltage-clamp experiments, cerebellar granule neurons exhibited at least two different K+ current components: a first transient component which is similar to an IA-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 microM, helothermine reduced the pharmacologically isolated IA-type current component in a voltage- and dose-dependent way, with a half-maximal inhibitory concentration (IC50) of 0.52 microM. A comparison between control and helothermine-modified peak transient currents shows a slowdown of activation and inactivation kinetics. The delayed-rectifier component inhibition was concentration dependent (IC50 = 0.86 microM) 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.