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Excitability parameters and sensitivity to anemone toxin ATX‐II in rat small diameter primary sensory neurones discriminated by Griffonia simplicifolia isolectin IB4
Author(s) -
Snape Alistair,
Pittaway James F.,
Baker Mark D.
Publication year - 2010
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2009.181107
Subject(s) - tetrodotoxin , depolarization , chemistry , neuroscience , sensory neuron , sensory system , sodium channel , stimulation , biophysics , membrane potential , biochemistry , biology , sodium , organic chemistry
Sensory neurone subtypes (≤ 25 μm apparent diameter) express a variety of Na + channels, where expression is linked to action potential duration, and associated with differential IB4‐lectin binding. We hypothesized that sensitivity to ATX‐II might also discriminate neurones and report that 1 μ m has negligible or small effects on action potentials in IB4 +ve, but dramatically increased action potential duration in IB4 −ve, neurones. The toxin did not act on tetrodotoxin‐resistant (TTX‐r) Na V 1.8 currents; discrimination was based on tetrodotoxin‐sensitive (TTX‐s) Na + channel expression. We also explored the effects of varying the holding potential on current threshold, and the effect of repetitive activation on action currents in IB4 +ve and −ve neurones. IB4 +ve neurones became more excitable with depolarization over the range −100 to −20 mV, but IB4 −ve neurones exhibited peak excitability near −55 mV, and were inexcitable at −20 mV. Eliciting action potentials at 2 Hz, we found that peak inward action current in IB4 +ve neurones was reduced, whereas changes in the current amplitude were negligible in most IB4 −ve neurones. Our findings are consistent with relatively toxin‐insensitive channels including Na V 1.7 being expressed in IB4 +ve neurones, whereas toxin sensitivity indicates that IB4 −ve neurones may express Na V 1.1 or Na V 1.2, or both. The retention of excitability at low membrane potentials, and the responses to repetitive stimulation are explained by the known preferential expression of Na V 1.8 in IB4 +ve neurones, and the reduction in action current in IB4 +ve neurones with repetitive stimulation supports a novel hypothesis explaining the slowing of conduction velocity in C‐fibres by the build‐up of Na + channel inactivation.