title: The toxin helothermine affects potassium currents in newborn rat cerebellar granule cells.
abstract: 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.
authors.affiliation: Istituto di Cibernetica e Biofisica, CNR, Genova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Nobile
authors.forename: V
authors.initials: V
authors.lastname: Magnelli
authors.forename: L
authors.initials: L
authors.lastname: Lagostena
authors.forename: J
authors.initials: J
authors.lastname: Mochca-Morales
authors.forename: L D
authors.initials: LD
authors.lastname: Possani
authors.forename: G
authors.initials: G
authors.lastname: Prestipino
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D002531:Cerebellum / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D008116:Lizards; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D010455:Peptides / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014688:Venoms / Q000494:pharmacology*
chemical_list: D010455:Peptides; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D014688:Venoms; C064223:helothermine; D015761:4-Aminopyridine