Inhibitory modulation by FMRFamide of the voltage‐gated sodium current in identified neurones in Lymnaea stagnalis.

A. B. Brussaard*, J. C. Lodder, A. ter Maat, T. A. de Vlieger, K. S. Kits

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

1. The putative neurotransmitter FMRFa (Phe‐Met‐Arg‐Phe‐amide) caused an inhibitory modulation of the voltage‐gated sodium current (INa) in central neurones, the peptidergic caudo dorsal cells (CDCs) of the mollusc Lymnaea stagnalis. FMRFa reduced INa at all command potentials tested (ranging from ‐35 to +20 mV), but the amplitude of the effect of FMRFa was voltage dependent, inhibition being stronger at more negative potentials (50 +/‐ 5% reduction at half‐maximal INa activation versus 25 +/‐ 8% at the peak of the I‐V curve). 2. INa current traces were well fitted by a Hodgkin & Huxley based model, using m3 activation kinetics and two time constants for inactivation. 3. The steady‐state inactivation curve of INa was characterized by half‐maximal inactivation at ‐42.5 +/‐ 1.81 mV and a slope factor of 4.6 +/‐ 0.28 mV. The fastest time constant of inactivation ran from 100 +/‐ 5 to 0.8 +/‐ 0.32 ms and the slower time constant from 505 +/‐ 45 to 4.8 +/‐ 1.40 ms in the range ‐40 to ‐5 mV. 4. FMRFa had no significant effect on either component of inactivation, nor on the voltage dependence of steady‐state inactivation, nor on the maximal conductance. 5. FMRFa affected the activation of INa. The activation time constant was increased, ranging from 0.75 +/‐ 0.050 to 0.22 +/‐ 0.017 ms under control and from 0.91 +/‐ 0.043 to 0.31 +/‐ 0.038 ms with FMRFa in the voltage range ‐25 to +5 mV. The steady‐state activation curve was shifted to less negative potentials: half‐maximal activation occurred at ‐26.5 +/‐ 1.2 mV under control and at 23.6 +/‐ 1.4 mV with FMRFa; the slope factor (4.6 +/‐ 1.4 mV in control experiments) was not affected. The combination of slower activation kinetics and a shift in the voltage dependence of activation in the Hodgkin & Huxley based model, adequately explained the reduction of INa by FMRFa. 6. The physiological consequence is that the spiking threshold is increased, causing an arrest of on‐going firing activity and a decrease in excitability. © 1991 The Physiological Society
Original languageEnglish
Pages (from-to)385-404
JournalJournal of Physiology - London
Volume441
Issue number1
DOIs
Publication statusPublished - 1 Sep 1991
Externally publishedYes

Cite this