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Anemone toxin (ATX II)-induced increase in persistent sodium current: effects on the firing properties of rat neocortical pyramidal neurones

Massimo Mantegazza, Silvana Franceschetti and Giuliano Avanzini

1. The experiments were performed on sensorimotor cortex using current-clamp intracellular recordings in layer V pyramidal neurones and whole-cell voltage-clamp recordings in dissociated pyramidal neurones. The intracellularly recorded neurones were classified on the basis of their firing characteristics as intrinsically bursting (IB) and regular spiking (RS). The RS neurones were further subdivided into adapting (RS_AD) or non-adapting (RS_NA), depending on the presence or absence of spike frequency adaptation. Since burst firing in neocortical pyramidal neurones has previously been suggested to depend on the persistent fraction of Na⁺ current (I_Na,p), pharmacological manipulations with drugs affecting I_Na inactivation have been employed.

2. ATX II, a toxin derived from Anemonia sulcata, selectively inhibited I_Na fast inactivation in dissociated neurones. In current-clamp experiments on neocortical slices, ATX II enhanced the naturally occurring burst firing in IB neurones and revealed the ability of RS_NA neurones to discharge in bursts, whereas in RS_AD neurones it increased firing frequency, without inducing burst discharges. During the ATX II effect, in all the three neuronal subclasses, episodes of a metastable condition occurred, characterized by long-lasting depolarizing shifts, triggered by action potentials, which were attributed to a peak in the toxin-induced inhibition of I_Na inactivation. The ATX II effect on IB and RS_NA neurones was compared with that induced by veratridine and iodoacetamide. Veratridine induced a small increase in the I_Na and a large shift to the left in the voltage dependence of I_Na activation. Accordingly, its major effect on firing characteristics was the induction of prolonged tonic discharges, associated with burst facilitation less pronounced than that induced by ATX II. The alkylating agent iodoacetamide was able to induce a selective small increase in the I_Na,p, with a similar but less pronounced effect than ATX II on firing behaviour.

3. The present results show that pharmacological manipulations capable of slowing down I_Na inactivation significantly enhance burst behaviour in IB neurones and promote burst firing in otherwise non-bursting RS_NA neurones. We suggest that IB and, to a lesser extent, RS_NA neurones are endowed with a relatively large fraction of I_Na>,p which, in physiological conditions, is sufficient to sustain bursting in IB but not in RS_NA neurones.

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