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221 110 110 1 1 Mario Nobile +39-10-6475500 Francesca Noceti Gianfranco Prestipino Lourival D. Possani Istituto di Cibernetica e Biofisica, CNR via De Marini 6 I-16149 Genova Italy Institute de Biotecnologia, UNAM 62271 Cuernavaca Mexico Abstract 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 Ca 2+ channels in cerebellar granule cells of newborn rats. Macroscopic currents, carried by 10 mM Ba 2+ , were measured in whole-cell configuration. The toxin at the saturating dose of 2.5 μM reversibly produced an ≈67% block of the voltage-dependent Ca 2+ 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 μM. The current block was practically voltage-independent, whereas the steady-state inactivation h ∞ was significantly affected by HLTx (≈10 mV). The toxin did not affect the activation and inactivation kinetics of the Ca 2+ current. Experiments with other Ca 2+ channel blockers showed that HLTx abolished ω-conotoxin GVIA-sensitive Ca 2+ currents, as well as ω-AgaIVA- and dihydropyridine-sensitive Ca 2+ 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 Ca 2+ current components.
Experimental Brain Research – Springer Journals
Published: Jun 1, 1996
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