Participation of Sodium Currents in Burst Generation and Control of Membrane Excitability in Mesencephalic Trigeminal Neurons

Abstract

Subthreshold sodium currents are important in sculpting neuronal discharge and have been implicated in production and/or maintenance of subthreshold membrane oscillations and burst generation in mesencephalic trigeminal neurons (Mes V). Moreover, recent data suggest that, in some CNS neurons, resurgent sodium currents contribute to production of high-frequency burst discharge. In the present study, we sought to determine more directly the participation of these currents during Mes V electrogenesis using the action potentialclamp method. In postnatal day 8 -14 rats, the whole-cell patch-clamp method was used to record sodium currents by subtraction in response to application of TTX in voltage-clamp mode using the action potential waveform as the command protocol. We found that TTX-sensitive sodium current is the main inward current flowing during the interspike interval, compared with the h-current (I h ) and calcium currents. Furthermore, in addition to the transient sodium current that flows during the upstroke of action potential, we show that resurgent sodium current flows at the peak of afterhyperpolarization and persistent sodium current flows in the middle of the interspike interval to drive high-frequency firing. Additionally, transient, resurgent, and persistent sodium current components showed voltage-and time-dependent slow inactivation, suggesting that slow inactivation of these currents can contribute to burst termination. The data suggest an important role for these components of the sodium current in Mes V neuron electrogenesis.

Multiple Sites for Generation of Ectopic Spontaneous Activity in Neurons of the Chronically Compressed Dorsal Root Ganglion

“…For type I SA with a bursting or irregular pattern, it was proposed that an oscillation triggered the first spike of each burst of discharges (Amir et al, 1999(Amir et al, , 2002b. The mechanism for SMPO might be attributable to the interaction between a tetrodotoxin (TTX)-sensitive Na ϩ conductance and a passive voltage-independent K ϩ conductance (Pedroarena et al, 1999;Amir et al, 2002a;Enomoto et al, 2006). However, it is not clear which currents might contribute to the different patterns of SA, or to the oscillation-induced triggering of action potentials.…”

Chewing rates among domestic dog breeds

“…According to neurophysiological investigators, the rhythm is produced by a population of brainstem cells known as a central timing network (CTN) or central rhythm generator (CRG); these cells form a subcomponent of a larger masticatory central pattern generator (CPG) network (Lund, 1991;Nakamura and Katakura, 1995). The traditional model of the masticatory CPG circuitry placed CTN cells within a fairly localized brainstem region (Nakamura and Katakura, 1995) but further investigations suggest that the rhythmicity is more diffusely represented (Enomoto et al, 2006;Lund et al, 1998;Nakamura et al, 1999;Tanaka et al, 1999;Tsuboi et al, 2003;Wu et al, 2001). Also, although the masticatory CPG is believed to be highly conserved (Lund et al, 1998;Wainwright, 2002), it is likely that many underappreciated taxonomic specificities in CTN design and location exist (Alfaro and Herrel, 2001).…”

Anticancer drug oxaliplatin induces acute cooling-aggravated neuropathy via sodium channel subtype Na V 1.6-resurgent and persistent current

“…Na v s generate the upstroke of the action potential (AP), but can also mediate persistent (I NaP ) and resurgent currents (I NaR ). I NaP enhances excitability around firing threshold (11,12) and mutations augmenting I NaP have been linked to human forms of epilepsy (Na V 1.1) (13), arrhythmia (Na V 1.5) (14), paramyotonia congenita (Na v 1.4) (15,16), and pain (Na v 1.7) (15,17). I NaR was first described in cerebellar Purkinje neurons and refers to a transient surge of inward sodium current occurring upon repolarization from a preceding period of strong depolarization (18).…”

“…I NaR was first described in cerebellar Purkinje neurons and refers to a transient surge of inward sodium current occurring upon repolarization from a preceding period of strong depolarization (18). Because of its unorthodox activation profile, I NaR is thought to promote burst discharge (11,12).…”