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Mechanism of the persistent sodium current activator veratridine-evoked Ca elevation: implication for epilepsy.
J Neurochem. 2009 Nov; 111(3):745-56.JN

Abstract

Although the role of Na(+) in several aspects of Ca(2+) regulation has already been shown, the exact mechanism of intracellular Ca(2+) concentration ([Ca(2+)](i)) increase resulting from an enhancement in the persistent, non-inactivating Na(+) current (I(Na,P)), a decisive factor in certain forms of epilepsy, has yet to be resolved. Persistent Na(+) current, evoked by veratridine, induced bursts of action potentials and sustained membrane depolarization with monophasic intracellular Na(+) concentration ([Na(+)](i)) and biphasic [Ca(2+)](i) increase in CA1 pyramidal cells in acute hippocampal slices. The Ca(2+) response was tetrodotoxin- and extracellular Ca(2+)-dependent and ionotropic glutamate receptor-independent. The first phase of [Ca(2+)](i) rise was the net result of Ca(2+) influx through voltage-gated Ca(2+) channels and mitochondrial Ca(2+) sequestration. The robust second phase in addition involved reverse operation of the Na(+)-Ca(2+) exchanger and mitochondrial Ca(2+) release. We excluded contribution of the endoplasmic reticulum. These results demonstrate a complex interaction between persistent, non-inactivating Na(+) current and [Ca(2+)](i) regulation in CA1 pyramidal cells. The described cellular mechanisms are most likely part of the pathomechanism of certain forms of epilepsy that are associated with I(Na,P). Describing the magnitude, temporal pattern and sources of Ca(2+) increase induced by I(Na,P) may provide novel targets for antiepileptic drug therapy.

Authors+Show Affiliations

Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Szigony, Hungary.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19719824

Citation

Fekete, Adám, et al. "Mechanism of the Persistent Sodium Current Activator Veratridine-evoked Ca Elevation: Implication for Epilepsy." Journal of Neurochemistry, vol. 111, no. 3, 2009, pp. 745-56.
Fekete A, Franklin L, Ikemoto T, et al. Mechanism of the persistent sodium current activator veratridine-evoked Ca elevation: implication for epilepsy. J Neurochem. 2009;111(3):745-56.
Fekete, A., Franklin, L., Ikemoto, T., Rózsa, B., Lendvai, B., Sylvester Vizi, E., & Zelles, T. (2009). Mechanism of the persistent sodium current activator veratridine-evoked Ca elevation: implication for epilepsy. Journal of Neurochemistry, 111(3), 745-56. https://doi.org/10.1111/j.1471-4159.2009.06368.x
Fekete A, et al. Mechanism of the Persistent Sodium Current Activator Veratridine-evoked Ca Elevation: Implication for Epilepsy. J Neurochem. 2009;111(3):745-56. PubMed PMID: 19719824.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanism of the persistent sodium current activator veratridine-evoked Ca elevation: implication for epilepsy. AU - Fekete,Adám, AU - Franklin,Laura, AU - Ikemoto,Takeshi, AU - Rózsa,Balázs, AU - Lendvai,Balázs, AU - Sylvester Vizi,E, AU - Zelles,Tibor, Y1 - 2009/08/31/ PY - 2009/9/2/entrez PY - 2009/9/2/pubmed PY - 2009/11/7/medline SP - 745 EP - 56 JF - Journal of neurochemistry JO - J Neurochem VL - 111 IS - 3 N2 - Although the role of Na(+) in several aspects of Ca(2+) regulation has already been shown, the exact mechanism of intracellular Ca(2+) concentration ([Ca(2+)](i)) increase resulting from an enhancement in the persistent, non-inactivating Na(+) current (I(Na,P)), a decisive factor in certain forms of epilepsy, has yet to be resolved. Persistent Na(+) current, evoked by veratridine, induced bursts of action potentials and sustained membrane depolarization with monophasic intracellular Na(+) concentration ([Na(+)](i)) and biphasic [Ca(2+)](i) increase in CA1 pyramidal cells in acute hippocampal slices. The Ca(2+) response was tetrodotoxin- and extracellular Ca(2+)-dependent and ionotropic glutamate receptor-independent. The first phase of [Ca(2+)](i) rise was the net result of Ca(2+) influx through voltage-gated Ca(2+) channels and mitochondrial Ca(2+) sequestration. The robust second phase in addition involved reverse operation of the Na(+)-Ca(2+) exchanger and mitochondrial Ca(2+) release. We excluded contribution of the endoplasmic reticulum. These results demonstrate a complex interaction between persistent, non-inactivating Na(+) current and [Ca(2+)](i) regulation in CA1 pyramidal cells. The described cellular mechanisms are most likely part of the pathomechanism of certain forms of epilepsy that are associated with I(Na,P). Describing the magnitude, temporal pattern and sources of Ca(2+) increase induced by I(Na,P) may provide novel targets for antiepileptic drug therapy. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/19719824/Mechanism_of_the_persistent_sodium_current_activator_veratridine_evoked_Ca_elevation:_implication_for_epilepsy_ L2 - https://doi.org/10.1111/j.1471-4159.2009.06368.x DB - PRIME DP - Unbound Medicine ER -