Dataset Information

Control of presynaptic function by a persistent Na(+) current.

ABSTRACT: Little is known about ion channels that regulate the graded, subthreshold properties of nerve terminals. Using the calyx of Held, we demonstrate here a large presynaptic persistent Na(+) current with unusually hyperpolarized activation voltage. This feature allowed the current to determine both the resting potential and resting conductance of the nerve terminal. Calyces express presynaptic glycine receptors whose activation depolarizes the synapse. We found that activation of the persistent Na(+) current was an essential component in the response to glycine. This Na(+) current originated at or very close to the terminal and was sustained even after trains of large spike-like depolarizations. Because Na(+) channels also underlie the presynaptic action potential, we conclude that their action both triggers and modulates exocytosis through control of presynaptic membrane voltage.

SUBMITTER: Huang H

PROVIDER: S-EPMC2657474 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Control of presynaptic function by a persistent Na(+) current.

Huang Hai H Trussell Laurence O LO

Neuron 20081201 6

Little is known about ion channels that regulate the graded, subthreshold properties of nerve terminals. Using the calyx of Held, we demonstrate here a large presynaptic persistent Na(+) current with unusually hyperpolarized activation voltage. This feature allowed the current to determine both the resting potential and resting conductance of the nerve terminal. Calyces express presynaptic glycine receptors whose activation depolarizes the synapse. We found that activation of the persistent Na(+ ...[more]

PMID: 19109905

Similar Datasets

Project description:There is clinical need to extend the understanding of epilepsy and to find novel approaches to treat this condition. Bang-sensitive (bs) Drosophila mutants, which exhibit reduced thresholds for seizure, offer an attractive possibility to combine tractable genetics, electrophysiology, and high-throughput screening. However, despite these advantages, the precise electrophysiological aberrations that contribute to seizure have not been identified in any bs mutant. Because of this, the applicability of Drosophila as a preclinical model has not yet been established. In this study, we show that electroshock of bs slamdance (sda) larvae was sufficient to induce extended seizure-like episodes. Whole cell voltage-clamp recordings from identified motoneurons (termed aCC and RP2) showed synaptic currents that were greatly increased in both amplitude and duration. Current-clamp recordings indicated that these inputs produced longer-lived plateau depolarizations and increased action potential firing in these cells. An analysis of voltage-gated currents in these motoneurons, in both first and third instar larvae, revealed a consistently increased persistent Na(+) current (I(Nap)) and a reduced Ca(2+) current in first instar larvae, which appeared normal in older third instar larvae. That increased I(Nap) may contribute to seizure-like activity is indicated by the observation that feeding sda larvae the antiepileptic drug phenytoin, which was sufficient to reduce I(Nap), rescued both seizure-like episode duration and synaptic excitation of motoneurons. In contrast, feeding of either anemone toxin, a drug that preferentially increases I(Nap), or phenytoin to wild-type larvae was sufficient to induce a bs behavioral phenotype. Finally, we show that feeding of phenytoin to gravid sda females was sufficient to both reduce I(Nap) and synaptic currents and rescue the bs phenotype in their larval progeny, indicating that a heightened predisposition to seizure may arise as a consequence of abnormal embryonic neural development.

Dataset Information

Control of presynaptic function by a persistent Na(+) current.

Publications

Control of presynaptic function by a persistent Na(+) current.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets