A subthreshold persistent sodium current mediates bursting in rat subfornical organ neurones
Article first published online: 12 AUG 2004
The Journal of Physiology
Volume 529, Issue 2, pages 359–371, December 2000
How to Cite
Washburn, D. L. S., Anderson, J. W. and Ferguson, A. V. (2000), A subthreshold persistent sodium current mediates bursting in rat subfornical organ neurones. The Journal of Physiology, 529: 359–371. doi: 10.1111/j.1469-7793.2000.00359.x
- Issue published online: 12 AUG 2004
- Article first published online: 12 AUG 2004
- (Received 19 June 2000; accepted after revision 10 August 2000)
- 1It is widely accepted that while release of amino acid neurotransmitters occurs with relatively high fidelity, peptidergic synapses require clustered bursts of action potentials for optimal transmitter release. Here we describe for the first time the occurrence and mechanisms of bursting by neurones in the subfornical organ (SFO), cells that utilize the peptide angiotensin II (ANG) in neurotransmission in autonomic pathways.
- 2In current clamp recording of isolated SFO neurones in vitro, 53 % (n= 74) showed either spontaneous or evoked burst-like discharge patterns. Bursts typically appeared as shifts in bistable membrane potential, with action potentials superimposed on a depolarizing afterpotential (DAP). Similarly, in vivo single unit recordings of identified SFO neurones showed that 9 of 15 neurones fired in bursts.
- 3The pattern of bursting, as well as duration of evoked DAPs was strongly dependent upon membrane potential, suggesting that the DAP contributes to burst generation. Based on our previous observation of calcium-sensing receptor (CaR)-activated bursts, we investigated the effects of NPS R-467, an allosteric agonist of the CaR, on evoked DAPs. NPS R-467 (1 μM) potentiated DAP duration throughout the voltage range tested.
- 4We observed a dependence of evoked DAPs upon Na+ channels, as shown by sensitivity to tetrodotoxin (0.5 μM) or reduction of external [Na+] from 140 to 40 |mM. The duration of DAPs suggested that a persistent Na+ current mediates these events. Voltage-clamp analysis revealed the presence of a subthreshold sodium current, INaP.
- 5Pharmacological blockade of INaP with 100 μM lidocaine reduced the duration of evoked DAPs, and inhibited bursting in SFO neurones. Facilitation of INaP with 10 nM anemone toxin (ATX) increased DAP duration and led to marked excitation of bursting cells. These data indicate that INaP is the main current underlying bursting in SFO neurones.
- 6Our observations of receptor-mediated facilitation of bursting by SFO neurones represents an intriguing mechanism through which the release of the peptide neurotransmitter ANG may be regulated.