Hyperforin modulates gating of P-type Ca2+ current in cerebellar Purkinje neurons
| Autor: | Timur Tsintsadze, Natalia Lozovaya, Alexander Fisunov, Michael Nöldner, Oleg Krishtal, Shyam Sunder Chatterjee |
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| Rok vydání: | 2000 |
| Předmět: |
Patch-Clamp Techniques
Calmodulin Physiology G protein Clinical Biochemistry Guanosine Gating Phloroglucinol Guanosine Diphosphate Second Messenger Systems Membrane Potentials chemistry.chemical_compound Bridged Bicyclo Compounds Purkinje Cells omega-Agatoxin IVA omega-Conotoxin GVIA Physiology (medical) Animals Rats Wistar Receptor Plants Medicinal biology Chemistry Terpenes Antagonist Calcium Channels P-Type Thionucleotides Calcium Channel Blockers Anti-Bacterial Agents Rats Hyperforin Biochemistry Guanosine 5'-O-(3-Thiotriphosphate) biology.protein Biophysics Ion Channel Gating Intracellular Hypericum |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0031-6768 |
| Popis: | Whole-cell, patch-clamp recordings from acutely isolated cerebellar Purkinje neurons demonstrate a two-stage modulation of P-type high-voltage-activated (HVA) Ca2+ current by a constituent of St. John's wort, hyperforin (0.04-0.8 microM). The first stage of modulation was voltage dependent and reversible. It comprised slow-down of the activation kinetics and a shift in the voltage dependence of P-current to more negative voltages. Hyperforin (0.8 microM) shifted the maximum of the current/voltage (I/V) relationship by -8+/-2 mV. The second, voltage-independent stage of modulation was manifested as a slowly developing inhibition of P-current that could not be reversed within the period of study. Neither form of modulation was abolished by intracellular guanosine 5'-O-(2-thiodiphosphate) (GDPPS) or guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) or by strong depolarising pre-pulses, indicating that modulation via guanine nucleotide-binding proteins (G proteins) is not involved in the observed phenomenon. Calmidazolium (0.5 microM), an antagonist of the intracellular Ca2+-binding protein calmodulin significantly inhibited the hyperforin-induced shift of the IIV curve maximum and the slow-down of the activation kinetics. It did not, however, affect the delayed inhibition of P-current, indicating that the two stages of modulation are mediated by separate mechanisms. |
| Databáze: | OpenAIRE |
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