Helothermine, a lizard venom toxin, inhibits calcium current in cerebellar granules.
Helothermine (HLTx), a 25.5-kDa peptide toxin isolated from the venom of the Mexican beaded lizard (Heloderma horridum horridum), was found to be an inhibitor of Ca2+ channels in cerebellar granule cells of newborn rats. Macroscopic currents, carried by 10 mM Ba2+, were measured in whole-cell configuration. The toxin at the saturating dose of 2.5 microM reversibly produced an approximately 67% block of the voltage-dependent Ca2+ current by a fast mechanism of action. The current inhibition and recovery were reached in less than 1 min. Inhibition was concentration-dependent, with a half-effective dose of 0.25 microM. The current block was practically voltage-independent, whereas the steady-state inactivation h infinity was significantly affected by HLTx (approximately 10 mV). The toxin did not affect the activation and inactivation kinetics of the Ca2+ current. Experiments with other Ca2+ channel blockers showed that HLTx abolished omega-cono-toxin GVIA-sensitive Ca2+ currents, as well as omega-Aga-IVA- and dihydropyridine-sensitive Ca2+ currents. These drugs had virtually no effect when HLTx was applied first. The present results indicate that HLTx produce a high-potency blockage of the three pharmacologically distinct Ca2+ current components.
Nobile
M
M
Istituto di Cibernetica e Biofisica, CNR, Genova, Italy.
Noceti
F
F
Prestipino
G
G
Possani
L D
LD
D000818:Animals; D002121:Calcium Channel Blockers / Q000633:toxicity*; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology; D008116:Lizards; D008978:Mollusk Venoms / Q000633:toxicity; D009474:Neurons / Q000187:drug effects; D009498:Neurotoxins / Q000633:toxicity*; D010455:Peptides / Q000633:toxicity*; D013111:Spider Venoms / Q000633:toxicity; D014688:Venoms / Q000737:chemistry*; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D008978:Mollusk Venoms; D009498:Neurotoxins; D010455:Peptides; D013111:Spider Venoms; D014688:Venoms; D020867:omega-Agatoxin IVA; C064223:helothermine; C038806:1,4-dihydropyridine; D020866:omega-Conotoxin GVIA