Resurgent Sodium Current and Action Potential Formation in Dissociated Cerebellar Purkinje Neurons

Abstract

Voltage-dependent sodium channels were studied in dissociated cerebellar Purkinje neurons from rats. In whole-cell recordings, a tetrodotoxin ( TTX )-sensitive inward current was elicited when the membrane was repolarized to voltages between Ϫ60 and Ϫ20 mV after depolarizations to ϩ30 mV long enough to produce maximal inactivation. At Ϫ40 mV, this "resurgent" current peaked in 8 msec and decayed with a time constant of 30 msec. With 50 mM sodium as a charge carrier, the resurgent current was on average ϳ120 pA. CA3 pyramidal neurons had no such current. The current may reflect recovery of inactivated channels through open states, because in Purkinje neurons (but not CA3 neurons) there was partial recovery from inactivation at Ϫ40 mV, coinciding with the rise of resurgent current. In single-channel recordings, individual channels gave openings corresponding to resurgent and conventional transient current. Action potentials were recorded from dissociated neurons under current clamp to investigate the role of the resurgent current in action potential formation. Purkinje neurons fired spontaneously at ϳ30 Hz. Hyperpolarization to Ϫ85 mV prevented spontaneous firing, and brief depolarization then induced all-or-none firing of conglomerate action potentials comprising three to four spikes. When conglomerate action potentials were used as command voltages in voltageclamp experiments, TTX-sensitive sodium current was elicited between spikes. The falling phase of an action potential is similar to voltage patterns that activate resurgent sodium current, and thus, resurgent sodium current likely contributes to the formation of conglomerate action potentials in Purkinje neurons.

Effects of SKF83959 on the excitability of hippocampal CA1 pyramidal neurons: a modeling study

“…In the present study, we demonstrated that modifying the Na + channel alone increases the rheobase current and consequently results in decreased excitability at both the soma and the dendrite, in agreement with previous reports [18][19][20] . In contrast with Na + channels, modifying the kdr channel alone can lead to a slight increase in neuronal excitability.…”

“…It has been suggested that such actions of SKF83959 on voltage-dependent ion channels likely occur via direct interactions with the affected ion channels rather than indirectly through D1-like receptors because of the drug's fast onset of action. Intuitively, inhibition of sodium currents results in a decrease in neuronal excitability [18][19][20] ; in contrast, a reduction of potassium currents may increase neuronal excitability in some conditions [21][22][23][24] . In regard to the HCN channel, the effect on neuronal excitability becomes more complex.…”

Ion channel regulation by β-secretase BACE1 – enzymatic and non-enzymatic effects beyond Alzheimer's disease

“…43,44,62 b4 cleavage and resurgent Na C currents Resurgent currents (I NaR ) have been first reported from cerebellar Purkinje cells, where they are mainly carried by Na v 1.6. 63 Mechanistically, they result from transient channel re-openings upon repolarization, when an unorthodox open-channel block, most likely exerted by parts of the b4 subunit, is relieved. 64,65 Since BACE1, which is known to cleave b4, is highly expressed in cerebellum, an obvious question was whether Purkinje cells from BACE1-deficient mice would exhibit altered firing pattern.…”

Persistent Changes in Spontaneous Firing of Purkinje Neurons Triggered by the Nitric Oxide Signaling Cascade

“…Both in vitro and in vivo, an individual Purkinje neuron maintains a distinct resting firing rate (Armstrong and Rawson, 1979;Häusser and Clark, 1997;Raman and Bean, 1997). A survey across many Purkinje neurons shows that some cells fire as slowly as 5 spikes/sec, whereas others fire as rapidly as 80 spikes/sec.…”