Essential Role of a Fast Persistent Inward Current in Action Potential Initiation and Control of Rhythmic Firing

Lee, R. H.; Heckman, C. J.

doi:10.1152/jn.2001.85.1.472

Cited by 130 publications

(135 citation statements)

References 18 publications

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“…It had previously been shown that phenytoin (Ն50 M) reduces the persistent sodium current in rat cortical neurons and enhances "slow adaptation" (Lampl et al 1998). In addition, it has been shown in cat spinal motoneurons that modest reductions in the persistent sodium current results in profound changes in the slope of the current-frequency relation and can lead to a failure of regular repetitive firing (Lee and Heckman 2001). Furthermore, based simply on the monotonic current-frequency relation of motoneurons, one would surmise that any agent or regimen that decreases a source of inward current should lead to lower firing rates (Powers and Binder 2001;Powers et al 1999).…”

Section: Discussionmentioning

confidence: 99%

“…Progressive inactivation of these inward currents would be expected to result in a decreased firing rate. Whereas the low-threshold calcium current often shows facilitation rather than inactivation (Bennett et al 1998;Svirskis and Hounsgaard 1997), the persistent sodium current has been shown to undergo slow inactivation in neocortical neurons (Fleidervish et al 1996) and spinal motoneurons (Lee and Heckman 2001).…”

Section: Introductionmentioning

confidence: 99%

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Contribution of Persistent Sodium Currents to Spike-Frequency Adaptation in Rat Hypoglossal Motoneurons

Zeng

Powers

Newkirk

et al. 2005

Journal of Neurophysiology

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. In response to constant current inputs, the firing rates of motoneurons typically show a continuous decline over time. The biophysical mechanisms underlying this process, called spike-frequency adaptation, are not well understood. Spike-frequency adaptation normally exhibits a rapid initial phase, followed by a slow, later phase that continues throughout the duration of firing. One possible mechanism mediating the later phase might be a reduction in the persistent sodium current (I NaP ) that has been shown to diminish the capacity of cortical pyramidal neurons and spinal motoneurons to sustain repetitive firing. In this study, we used the anticonvulsant phenytoin to reduce the I NaP of juvenile rat hypoglossal motoneurons recorded in brain stem slices, and we examined the consequences of a reduction in I NaP on the magnitude and time course of spike-frequency adaptation. Adding phenytoin to the bathing solution (Ն50 M) generally produced a marked reduction in the persistent inward currents (PICs) recorded at the soma in response to slow, voltage-clamp triangular ramp commands (Ϫ70 to 0 mV and back). However, the same concentrations of phenytoin appeared to have no significant effect on spike-frequency adaptation even though the phenytoin often augmented the reduction in action potential amplitude that occurs during repetitive firing. The surprising finding that the reduction of a source of sustained inward current had no appreciable effect on the pattern of spike generation suggests that several types of membrane channels must act cooperatively to insure that these motoneurons can generate the sustained repetitive firing required for long-lasting motor behaviors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Contribution of Persistent Sodium Currents to Spike-Frequency Adaptation in Rat Hypoglossal Motoneurons

Zeng

Powers

Newkirk

et al. 2005

Journal of Neurophysiology

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“…The PICs in motoneurons are composed of I NaP (Nishimura et al, 1989;Hsiao et al, 1998;Lee and Heckman, 2001;Li and Bennett, 2003;Powers and Binder, 2003;Tazerart et al, 2007) and calcium components (Schwindt and Crill, 1980;Hounsgaard and Kiehn, 1989;Heckman et al, 2008a;Carlin et al, 2009). PICs generating plateaus in motoneurons of adult cats (Hounsgaard et al, 1984), mice (Carlin et al, 2000b), rats (Li and Bennett, 2003), turtles (Hounsgaard and Mintz, 1988), and frogs (Perrier and Tresch, 2005) are predominantly mediated by L-type calcium channels and to a lesser extent by I NaP Harvey et al, 2006).…”

Section: Plateau Potentials Rely On I Canmentioning

confidence: 99%

Sodium-Mediated Plateau Potentials in Lumbar Motoneurons of Neonatal Rats

et al. 2013

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The development and the ionic nature of bistable behavior in lumbar motoneurons were investigated in rats. One week after birth, almost all (ϳ80%) ankle extensor motoneurons recorded in whole-cell configuration displayed self-sustained spiking in response to a brief depolarization that emerged when the temperature was raised Ͼ30°C. The effect of L-type Ca 2ϩ channel blockers on self-sustained spiking was variable, whereas blockade of the persistent sodium current (I NaP ) abolished them. When hyperpolarized, bistable motoneurons displayed a characteristic slow afterdepolarization (sADP). The sADPs generated by repeated depolarizing pulses summed to promote a plateau potential. The sADP was tightly associated with the emergence of Ca 2ϩ spikes. Substitution of extracellular Na ϩ or chelation of intracellular Ca 2ϩ abolished both sADP and the plateau potential without affecting Ca 2ϩ spikes. These data suggest a key role of a Ca

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“…It activates below the spike threshold with a time constant of the order of the millisecond (Crill, 1996). It amplifies synaptic inputs (Schwindt and Crill, 1995) and promotes spike initiation (Kuo et al, 2006), repetitive firing (Lee and Heckman, 2001;Harvey et al, 2006a), and bursting (Wu et al, 2005). It may also enhance subthreshold resonances (Gutfreund et al, 1995;Hutcheon et al, 1996;Hutcheon and Yarom, 2000).…”

Section: Introductionmentioning

confidence: 99%

Resonant or Not, Two Amplification Modes of Proprioceptive Inputs by Persistent Inward Currents in Spinal Motoneurons

Manuel¹,

Meunier²,

Donnet³

et al. 2007

J. Neurosci.

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Why do motoneurons possess two persistent inward currents (PICs), a fast sodium current and a slow calcium current? To answer this question, we replaced the natural PICs with dynamic clamp-imposed artificial PICs at the soma of spinal motoneurons of anesthetized cats. We investigated how PICs with different kinetics (1-100 ms) amplify proprioceptive inputs. We showed that their action depends on the presence or absence of a resonance created by the I h current. In resonant motoneurons, a fast PIC enhances the resonance and amplifies the dynamic component of Ia inputs elicited by ramp-and-hold muscle stretches. This facilitates the recruitment of these motoneurons, which likely innervate fast contracting motor units developing large forces, e.g., to restore balance or produce ballistic movements. In nonresonant motoneurons, in contrast, a fast PIC easily triggers plateau potentials, which leads to a dramatic amplification of the static component of Ia inputs. This likely facilitates the recruitment of these motoneurons, innervating mostly slowly contracting and fatigue-resistant motor units, during postural activities. Finally, a slow PIC may switch a resonant motoneuron to nonresonant by counterbalancing I h , thus changing the action of the fast PIC. A modeling study shows that I h needs to be located on the dendrites to create the resonance, and it predicts that dendritic PICs amplify synaptic input in the same manner as somatic PICs.

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Essential Role of a Fast Persistent Inward Current in Action Potential Initiation and Control of Rhythmic Firing

Cited by 130 publications

References 18 publications

Contribution of Persistent Sodium Currents to Spike-Frequency Adaptation in Rat Hypoglossal Motoneurons

Contribution of Persistent Sodium Currents to Spike-Frequency Adaptation in Rat Hypoglossal Motoneurons

Sodium-Mediated Plateau Potentials in Lumbar Motoneurons of Neonatal Rats

Resonant or Not, Two Amplification Modes of Proprioceptive Inputs by Persistent Inward Currents in Spinal Motoneurons

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