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

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1. The experiments were performed on sensorimotor cortex using current-clamp intracellular recordings in layer V pyramidal neurons and whole-cell voltage-clamp recordings in dissociated pyramidal neurons. The intracellularly recorded neurons were classified on the basis of their firing characteristics as intrinsically bursting (IB) and regular spiking (RS). The RS neurons were further subdivided into adapting (RSAD) or non-adapting (RSNA), depending on the presence or absence of spike frequency adaptation. Since burst firing in neocortical pyramidal neurons has previously been suggested to depend on the persistent fraction of Na+ current (INa, p), pharmacological manipulations with drugs affecting INa inactivation have been employed. 2. ATX II, a toxin derived from Anemonia sulcata, selectively inhibited INa fast inactivation in dissociated neurons. In current-clamp experiments on neocortical slices, ATX II enhanced the naturally occurring burst firing in IB neurons and revealed the ability of RSNA neurons to discharge in bursts, whereas in RSAD neurons 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 INa inactivation. The ATX II effect on IB and RSNA neurons was compared with that induced by veratridine and iodoacetamide. Veratridine induced a small increase in the INa and a large shift to the left in the voltage dependence of INa 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 INa,p, with a similar but less pronounced effect than ATX II on firing behavior. 3. The present results show that pharmacological manipulations capable of slowing down INa inactivation significantly enhance burst behavior in IB neurons and promote burst firing in otherwise non-bursting RSNA neurons. We suggest that IB and, to a lesser extent, RSNA neurons are endowed with a relatively large fraction of INa,p which, in physiological conditions, is sufficient to sustain bursting in IB but not in RSNA neurons.