Effects of ouabain on respiratory rhythm generation in brainstem-spinal cord preparation from newborn rats and in decerebrate and arterially perfused in situ preparation from juvenile rats

Tsuzawa, Kayo; Yazawa, Itaru; Shakuo, Tomoharu; Ikeda, Keiko; Kawakami, Kiyoshi; Onimaru, Hiroshi

doi:10.1016/j.neuroscience.2014.12.006

Cited by 4 publications

(3 citation statements)

References 37 publications

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“…Using two different stimulation methods (pharmacological and sensory), we found that sodium pump blockade increased the frequency of rhythmic locomotor-like activity, whereas pump activation had the opposite effect. Similar effects of ouabain have been reported for the leech heartbeat CPG ( Tobin and Calabrese, 2005 ; Kueh et al, 2016 ), the rat respiratory CPG ( Tsuzawa et al, 2015 ), and dopaminergic midbrain networks in the rat ( Johnson et al, 1992 ). Ouabain's effects on rhythm frequency could be due to the removal of a tonic, negative contribution of the pump to the RMP, thereby depolarizing specific neurons involved in rhythm generation.…”

Section: Discussionsupporting

confidence: 77%

“…The role of the sodium pump in the rhythm-generating networks of the mammalian brainstem and spinal cord is less well described. In the brainstem respiratory network, termination of respiratory-related bursts is partly mediated by enhanced pump current, among other Na + -dependent outward currents ( Krey et al, 2010 ; Tsuzawa et al, 2015 ). Within the rat spinal cord, where α3-containing sodium pump expression is high ( Watts et al, 1991 ), blockade of the sodium pump disrupts disinhibited bursting induced by strychnine and bicuculline, causing activity to first become sporadic and then cease altogether ( Ballerini et al, 1997 ).…”

Section: Introductionmentioning

confidence: 99%

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Sodium Pumps Mediate Activity-Dependent Changes in Mammalian Motor Networks

et al. 2016

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Ubiquitously expressed sodium pumps are best known for maintaining the ionic gradients and resting membrane potential required for generating action potentials. However, activity- and state-dependent changes in pump activity can also influence neuronal firing and regulate rhythmic network output. Here we demonstrate that changes in sodium pump activity regulate locomotor networks in the spinal cord of neonatal mice. The sodium pump inhibitor, ouabain, increased the frequency and decreased the amplitude of drug-induced locomotor bursting, effects that were dependent on the presence of the neuromodulator dopamine. Conversely, activating the pump with the sodium ionophore monensin decreased burst frequency. When more “natural” locomotor output was evoked using dorsal-root stimulation, ouabain increased burst frequency and extended locomotor episode duration, whereas monensin slowed and shortened episodes. Decreasing the time between dorsal-root stimulation, and therefore interepisode interval, also shortened and slowed activity, suggesting that pump activity encodes information about past network output and contributes to feedforward control of subsequent locomotor bouts. Using whole-cell patch-clamp recordings from spinal motoneurons and interneurons, we describe a long-duration (∼60 s), activity-dependent, TTX- and ouabain-sensitive, hyperpolarization (∼5 mV), which is mediated by spike-dependent increases in pump activity. The duration of this dynamic pump potential is enhanced by dopamine. Our results therefore reveal sodium pumps as dynamic regulators of mammalian spinal motor networks that can also be affected by neuromodulatory systems. Given the involvement of sodium pumps in movement disorders, such as amyotrophic lateral sclerosis and rapid-onset dystonia parkinsonism, knowledge of their contribution to motor network regulation also has considerable clinical importance.SIGNIFICANCE STATEMENT The sodium pump is ubiquitously expressed and responsible for at least half of total brain energy consumption. The pumps maintain ionic gradients and the resting membrane potential of neurons, but increasing evidence suggests that activity- and state-dependent changes in pump activity also influence neuronal firing. Here we demonstrate that changes in sodium pump activity regulate locomotor output in the spinal cord of neonatal mice. We describe a sodium pump-mediated afterhyperpolarization in spinal neurons, mediated by spike-dependent increases in pump activity, which is affected by dopamine. Understanding how sodium pumps contribute to network regulation and are targeted by neuromodulators, including dopamine, has clinical relevance due to the role of the sodium pump in diseases, including amyotrophic lateral sclerosis, parkinsonism, epilepsy, and hemiplegic migraine.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Sodium Pumps Mediate Activity-Dependent Changes in Mammalian Motor Networks

et al. 2016

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“…For example, pump-mediated AHPs have been reported in the sensory neurons of a range of species including insects (French 1989), lamprey (Parker et al 1996), leech (Arganda et al 2007;Baylor and Nicholls 1969;Scuri et al 2002), crayfish (Nakajima and Takahashi 1966;Sokolove and Cooke 1971), frogs (Davidoff and Hackman 1980;Kobayashi et al 1997), horseshoe crabs (Smith et al 1968), and rats (Gordon et al 1990). Similar posttetanic AHP mechanisms mediated by the Na ϩ pump have also been found in the interneurons of numerous species including the leech (Tobin and Calabrese 2005), Aplysia (Carpenter and Alving 1968;Pinsker and Kandel 1969), and rats (Darbon et al 2002(Darbon et al , 2003Krey et al 2010;Tsuzawa et al 2015). Finally, the motoneurons of diverse species have also been shown to display a spike-dependent, pump-mediated hyperpolarization, including in the motor axons of lizards (Morita et al1993), guinea pigs (del Negro et al 1999), rats (Ballerini et al 1997;Gage and Hubbard 1966), and humans (Kiernan et al 2004;Vagg et al 1998).…”

Section: Phylogenetically Conserved Functions Of Dynamic Na ϩ Pumpsmentioning

confidence: 60%

Sodium pump regulation of locomotor control circuits

Picton

Zhang

Sillar

2017

Journal of Neurophysiology

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Sodium pumps are ubiquitously expressed membrane proteins that extrude three Na ions in exchange for two K ions, using ATP as an energy source. Recent studies have illuminated additional, dynamic roles for sodium pumps in regulating the excitability of neuronal networks in an activity-dependent fashion. We review their role in a novel form of short-term memory within rhythmic locomotor networks. The data we review derives mainly from recent studies on tadpoles and neonatal mice. The role and underlying mechanisms of pump action broadly match previously published data from an invertebrate, the larva. We therefore propose a highly conserved mechanism by which sodium pump activity increases following a bout of locomotion. This results in an ultraslow afterhyperpolarization (usAHP) of the membrane potential that lasts around 1 min, but which only occurs in around half the network neurons. This usAHP in turn alters network excitability so that network output is reduced in a locomotor interval-dependent manner. The pumps therefore confer on spinal locomotor networks a temporary memory trace of recent network performance.

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