Na+/K+ pump interacts with the h-current to control bursting activity in central pattern generator neurons of leeches

The dynamics of different ionic currents shape the bursting activity of neurons and networks that control motor output. Despite being ubiquitous in all animal cells, the contribution of the Na+/K+ pump current to such bursting activity has not been well studied. We used monensin, a Na+/H+ antiporter, to examine the role of the pump on the bursting activity of oscillator heart interneurons in leeches. When we stimulated the pump with monensin, the period of these neurons decreased significantly, an effect that was prevented or reversed when the h-current was blocked by Cs+. The decreased period could also occur if the pump was inhibited with strophanthidin or K+-free saline. Our monensin results were reproduced in model, which explains the pump’s contributions to bursting activity based on Na+ dynamics. Our results indicate that a dynamically oscillating pump current that interacts with the h-current can regulate the bursting activity of neurons and networks. DOI: http://dx.doi.org/10.7554/eLife.19322.001

• Publication year

  2016

• Venue

  eLife

• Publication date

  2016-09-02

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.7554/eLife.19322PMID 27588351PMCID 5010386
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Electrogenic properties of the Na⁺/K⁺ ATPase control transitions between normal and pathological brain states.

  2015cited by this paper
• Mechanisms underlying the activity-dependent regulation of locomotor network performance by the Na+ pump

  2015influential reference
• Variation in motor output and motor performance in a centrally generated motor pattern.

  2014cited by this paper
• Identifying Crucial Parameter Correlations Maintaining Bursting Activity

  2014cited by this paper
• Sodium and calcium mechanisms of rhythmic bursting in excitatory neural networks of the pre‐Bötzinger complex: a computational modelling study

  2013cited by this paper
• High Prevalence of Multistability of Rest States and Bursting in a Database of a Model Neuron

  2013cited by this paper
• A Sodium-Pump-Mediated Afterhyperpolarization in Pyramidal Neurons

  2013cited by this paper
• From lamprey to salamander: an exploratory modeling study on the architecture of the spinal locomotor networks in the salamander

  2013cited by this paper
• Bistability of silence and seizure-like bursting.

  2013cited by this paper
• Targeting a neuropeptide to discrete regions of the motor arborizations of a single neuron

  2012cited by this paper
• Intracellular Na(+) and metabolic modulation of Na/K pump and excitability in the rat suprachiasmatic nucleus neurons.

  2012influential reference
• Short-term memory of motor network performance via activity-dependent potentiation of Na+/K+ pump function.

  2012cited by this paper
• Optical probing of sodium dynamics in neurons and astrocytes

  2011cited by this paper
• Ionic Dynamics Mediate Spontaneous Termination of Seizures and Postictal Depression State

  2011cited by this paper
• Brain Research

  2009cited by this paper
• The H‐current secures action potential transmission at high frequencies in rat cerebellar parallel fibers

  2009cited by this paper
• Spike integration and cellular memory in a rhythmic network from Na+/K+ pump current dynamics

  2009cited by this paper
• Persistent Na+ and K+-Dominated Leak Currents Contribute to Respiratory Rhythm Generation in the Pre-Bötzinger Complex In Vitro

  2008cited by this paper
• A central pattern generator producing alternative outputs: pattern, strength, and dynamics of premotor synaptic input to leech heart motor neurons.

  2007cited by this paper
• Hybrid systems analysis of the control of burst duration by low-voltage-activated calcium current in leech heart interneurons.

  2006cited by this paper
• Na+‐K+ Pump Stimulation Improves Contractility in Damaged Muscle Fibers

  2005cited by this paper
• Myomodulin increases Ih and inhibits the NA/K pump to modulate bursting in leech heart interneurons.

  2005cited by this paper
• Voltage dependence of the rheogenic Na+/K+ ATPase in the membrane of oocytes ofXenopus laevis

  2005cited by this paper
• Using a Hybrid Neural System to Reveal Regulation of Neuronal Network Activity by an Intrinsic Current

  2004influential reference
• Acetyl-L-carnitine induces a sustained potentiation of the afterhyperpolarization.

  2004cited by this paper
• Unmyelinated axons in the rat hippocampus hyperpolarize and activate an H current when spike frequency exceeds 1 Hz

  2003cited by this paper
• Intrinsic bursting activity in the pre-Bötzinger Complex: Role of persistent sodium and potassium currents

  2003cited by this paper
• Overexpression of a Hyperpolarization-Activated Cation Current (Ih) Channel Gene Modifies the Firing Activity of Identified Motor Neurons in a Small Neural Network

  2003cited by this paper
• Voltage-sensitive ion channels in rhythmic motor systems.

  2002cited by this paper
• Persistent sodium current, membrane properties and bursting behavior of pre-bötzinger complex inspiratory neurons in vitro.

  2002cited by this paper
• Phase relationships between segmentally organized oscillators in the leech heartbeat pattern generating network.

  2002cited by this paper
• Bursting in Leech Heart Interneurons: Cell-Autonomous and Network-Based Mechanisms

  2002influential reference
• Action potential threshold of hippocampal pyramidal cells in vivo is increased by recent spiking activity.

  2001cited by this paper
• A model of slow plateau-like oscillations based upon the fast Na+ current in a window mode

  2001cited by this paper
• Electrophysiology of the sodium-potassium-ATPase in cardiac cells.

  2001cited by this paper
• A Model of a Segmental Oscillator in the Leech Heartbeat Neuronal Network

  2001influential reference
• Central pattern generators and the control of rhythmic movements.

  2001cited by this paper
• Effects of the Na / H exchanger monensin on intracellular pH in astroglia *

  2000influential reference
• Oscillatory behaviors in pharmacologically isolated heart interneurons from the medicinal leech

  2000cited by this paper
• Role of the Na/H antiport in pH-dependent cell death in pulmonary artery endothelial cells.

  2000cited by this paper
• Prevention of Monensin-Induced Hyperpolarization in NG108-15 Cells

  2000influential reference
• Models of respiratory rhythm generation in the pre-Bötzinger complex. I. Bursting pacemaker neurons.

  1999cited by this paper
• Pharmacological actions of monovalent ionophores on spontaneously beating rabbit sino-atrial nodal cells.

  1999cited by this paper
• Axonal and glial currents activated during the post-tetanic hyperpolarization in non-myelinated nerve

  1998influential reference
• Transduction of temporal patterns by single neurons

  1998cited by this paper
• Synchronized oscillations in the inferior olive are controlled by the hyperpolarization-activated cation current I(h).

  1997cited by this paper
• Pharmacological block of the electrogenic sodium pump disrupts rhythmic bursting induced by strychnine and bicuculline in the neonatal rat spinal cord.

  1997cited by this paper
• Activation of Intrinsic and Synaptic Currents in Leech Heart Interneurons by Realistic Waveforms

  1996influential reference
• Sodium‐‐potassium pump current in rabbit sino‐atrial node cells.

  1996cited by this paper
• Principles of rhythmic motor pattern generation.

  1996cited by this paper
• Coupling potentials in CA1 neurons during calcium-free-induced field burst activity

  1995cited by this paper
• Neural networks that co-ordinate locomotion and body orientation in lamprey.

  1995cited by this paper
• Potassium and calcium channel dependence of bursting in cultured neuronal networks.

  1994cited by this paper
• A persistent sodium current contributes to oscillatory activity in heart interneurons of the medicinal leech

  1994cited by this paper
• Generation of beta-amyloid in the secretory pathway in neuronal and nonneuronal cells.

  1993cited by this paper
• Pacemaker mechanisms in cardiac tissue.

  1993cited by this paper
• Modulatory effects of FMRF-NH2 on outward currents and oscillatory activity in heart interneurons of the medicinal leech

  1992cited by this paper
• Burst firing in dopamine neurons induced by N-methyl-D-aspartate: role of electrogenic sodium pump.

  1992cited by this paper
• Evidence that acetylcholine is an inhibitory transmitter of heart interneurons in the leech.

  1992cited by this paper
• Na+-H+ antiport and monensin effects on cytosolic pH and iodide transport in FRTL-5 rat thyroid cells.

  1992cited by this paper
• Ionic currents of the lateral pyloric neuron of the stomatogastric ganglion of the crab.

  1992cited by this paper
• Synchronized oscillatory activity in leech neurons induced by calcium channel blockers.

  1991cited by this paper
• Charge translocation by the Na,K-pump: I. Kinetics of local field changes studied by time-resolved fluorescence measurements

  1991cited by this paper
• Serotonin depresses the after-hyperpolarization through the inhibition of the Na+/K+ electrogenic pump in T sensory neurones of the leech.

  1991cited by this paper
• Two inward currents and the transformation of low‐frequency oscillations of rat and cat thalamocortical cells.

  1991cited by this paper
• Calcium currents and graded synaptic transmission between heart interneurons of the leech

  1991influential reference
• Electrogenic pump (Na+/K(+)-ATPase) activity in rat optic nerve.

  1990cited by this paper
• Dependence of Na-K pump current on internal Na+ in mammalian cardiac myocytes.

  1990cited by this paper
• Electrophysiological effects of monensin, a sodium ionophore, on cardiac Purkinje fibers.

  1990influential reference
• A hyperpolarization-activated inward current in heart interneurons of the medicinal leech

  1989influential reference
• Evidence for the activation of an electrogenic sodium pump in leech retzius neurons following kainate depolarization

  1986influential reference
• Intracellular alkalinization potentiates slow inward current and prolonged bursting in a molluscan neuron.

  1983cited by this paper
• Effects of monensin on the response to low potassium in a molluscan muscle, the radular protractor of Busycon canaliculatum.

  1982influential reference
• Characterization of the electrogenic sodium pump in cardiac Purkinje fibres

  1980cited by this paper
• Activation of electrogenic Na+/K+ exchange by extracellular K+ in canine cardiac Purkinje fibers.

  1980cited by this paper
• Mechanism of monensin-induced hyperpolarization of neuroblastoma-glioma hybrid NG108-15.

  1979influential reference
• Rhythmic swimming activity in neurones of the isolated nerve cord of the leech.

  1976cited by this paper
• The role of electrogenic sodium pumping in the response of smooth muscle to acetylcholine

  1973cited by this paper
• Conductance changes, an electrogenic pump and the hyperpolarization of leech neurones following impulses

  1973cited by this paper
• Electrogenic Sodium Pump in Squid Giant Axon

  1973cited by this paper
• Intracellular sodium activity and the sodium pump in snail neurones

  1972influential reference
• Electrogenic sodium pump in nerve and muscle cells.

  1972influential reference
• Electrogenic Ion Pumping in Nervous Tissue

  1971cited by this paper
• Inhibition of Impulse Activity in a Sensory Neuron by an Electrogenic Pump

  1971influential reference
• Seawater Teleosts: Evidence for a Sodium-Potassium Exchange in the Branchial Sodium-Excreting Pump

  1969cited by this paper
• After‐effects of nerve impulses on signalling in the central nervous system of the leech

  1969influential reference
• On the electrogenic sodium pump in mammalian non‐myelinated nerve fibres and its activation by various external cations

  1968influential reference
• A Role for the Sodium Pump in Photoreception in Limulus

  1968influential reference
• A Contribution of an Electrogenic Na+ Pump to Membrane Potential in Aplysia Neurons

  1968influential reference
• The behaviour of the sodium pump in red cells in the absence of external potassium

  1967cited by this paper
• The origin of the post‐tetanic hyperpolarization of mammalian motor nerve terminals

  1966cited by this paper
• Post‐tetanic hyperpolarization and electrogenic Na pump in stretch receptor neurone of crayfish

  1966cited by this paper
• AN ELECTROGENIC SODIUM PUMP IN SNAIL NERVE CELLS.

  1965cited by this paper
• Active transport of cations in giant axons from Sepia and Loligo

  1955cited by this paper
• Neural networks that co-ordinate locomotion and body orientation in lamprey

  year unknowncited by this paper
• Frontiers in Neural Circuits Neural Circuits Materials and Methods

  year unknowncited by this paper
• Frontiers in Neural Circuits Neural Circuits

  year unknowncited by this paper

• The electrogenicity of the Na+/K+-ATPase poses challenges for computation in highly active spiking cells

  2025cites this paper
• Computer simulations of a dynamic sodium pump-mediated hyperpolarization and short-term motor memory in the spinal locomotor network of Xenopus frog tadpoles

  2025cites this paper
• Homeostatic regulation of a motor circuit through temperature sensing rather than activity sensing.

  2025cites this paper
• Differentiating the contributions of Na+/K+ pump current and persistent Na+ current in simulated voltage-clamp experiments.

  2025cites this paper
• Homeostatic regulation of a motor circuit through temperature sensing rather than activity sensing

  2025cites this paper
• The influence of hyperpolarization-activated cation current on conduction delay and failure of action potentials along axon related to abnormal functions

  2024cites this paper
• Multistability of bursting rhythms in a half-center oscillator and the protective effects of synaptic inhibition

  2024cites this paper
• The Na+/K+-ATPase generically enables deterministic bursting in class I neurons by shearing the spike-onset bifurcation structure

  2024cites this paper
• Degenerate neuronal and circuit mechanisms important for generating rhythmic motor patterns.

  2024cites this paper
• Dynamics of antiphase bursting modulated by the inhibitory synaptic and hyperpolarization-activated cation currents

  2024cites this paper
• Bursting Dynamics Based on the Persistent Na+ and Na+/K+ Pump Currents: A Dynamic Clamp Approach

  2023cites this paper
• Temporal dynamics of Na/K pump mediated memory traces: insights from conductance-based models of Drosophila neurons

  2023cites this paper
• Rapid cold hardening increases axonal Na+/K+-ATPase activity and enhances performance of a visual motion detection circuit in Locusta migratoria.

  2022cites this paper
• Optogenetic Low-Frequency Stimulation of Principal Neurons, but Not Parvalbumin-Positive Interneurons, Prevents Generation of Ictal Discharges in Rodent Entorhinal Cortex in an In Vitro 4-Aminopyridine Model

  2022cites this paper
• Regulation of Potassium and Chloride Concentrations in Nervous Tissue as a Method of Anticonvulsant Therapy

  2022cites this paper
• Neuronal morphology enhances robustness to perturbations of channel densities

  2022cites this paper
• Bimodal modulation of short-term motor memory via dynamic sodium pumps in a vertebrate spinal cord

  2022cites this paper
• Organelle calcium-derived voltage oscillations in pacemaker neurons drive the motor program for food-seeking behavior in Aplysia

  2021cites this paper
• Interactions among diameter, myelination, and the Na/K pump affect axonal resilience to high-frequency spiking

  2021cites this paper
• Organelle calcium-derived voltage oscillations in pacemaker neurons drive food-seeking behavior in Aplysia

  2021cites this paper
• Dynamics of subthreshold and suprathreshold resonance modulated by hyperpolarization-activated cation current in a bursting neuron

  2021cites this paper
• Dynamics of ramping bursts in a respiratory neuron model

  2021cites this paper
• Comodulation of h- and Na+/K+ Pump Currents Expands the Range of Functional Bursting in a Central Pattern Generator by Navigating between Dysfunctional Regimes

  2021cites this paper
• Muscarinic regulation of the neuronal Na+/K+‐ATPase in rat hippocampus

  2021cites this paper
• Interactions between Diameter, Myelination and the Na/K pump Affect Axonal Resilience to High Frequency Spiking

  2021cites this paper
• 30th Annual Computational Neuroscience Meeting: CNS*2021–Meeting Abstracts

  2021cites this paper
• Dynamical mechanism for conduction failure behavior of action potentials related to pain information transmission

  2020cites this paper
• Co‐modulation of the Na+/K+ pump and hyperpolarization‐activated currents as a mechanism for robust neuromodulation

  2020cites this paper
• The M-current works in tandem with the persistent sodium current to set the speed of locomotion

  2020cites this paper
• Contributions of h- and Na+/K+ Pump Currents to the Generation of Episodic and Continuous Rhythmic Activities

  2020cites this paper
• Neural Interactions in Developing Rhythmogenic Spinal Networks: Insights From Computational Modeling

  2020cites this paper
• Dynamics of episodic and continuous rhythmic activities from a developing central pattern generator

  2020cites this paper
• It takes two to tango: M-current swings with the persistent sodium current to set the speed of locomotion

  2020cites this paper
• Regulation of Neuronal Na+/K+-ATPase by Specific Protein Kinases and Protein Phosphatases

  2019cites this paper
• New channel lineup in spinal circuits governing locomotion

  2019cites this paper
• Differential contributions of Ca2+‐activated K+ channels and Na+/K+‐ATPases to the generation of the slow afterhyperpolarization in CA1 pyramidal cells

  2018cites this paper
• Developmental changes in spinal neuronal properties, motor network configuration, and neuromodulation at free-swimming stages of Xenopus tadpoles.

  2018cites this paper
• Propensity for Bistability of Bursting and Silence in the Leech Heart Interneuron

  2018cites this paper
• Control of Xenopus Tadpole Locomotion via Selective Expression of Ih in Excitatory Interneurons

  2018cites this paper
• Na+/K+-pump and neurotransmitter membrane receptors

  2018cites this paper
• Analytical CPG model driven by limb velocity input generates accurate temporal locomotor dynamics

  2018cites this paper
• 27th Annual Computational Neuroscience Meeting (CNS*2018): Part Two

  2018influential citation
• Control of transitions between locomotor-like and paw shake-like rhythms in a model of a multistable central pattern generator.

  2018cites this paper
• Vertical Finger Displacement Is Reduced in Index Finger Tapping During Repeated Bout Rate Enhancement.

  2017cites this paper
• Sodium pump regulation of locomotor control circuits.

  2017cites this paper
• Sodium Pumps Mediate Activity-Dependent Changes in Mammalian Motor Networks

  2017cites this paper
• The roles of dopamine and the sodium pump in the spinal control of locomotion

  2017influential citation
• Selective ligands for Na+/K+‐ATPase &agr; isoforms differentially and cooperatively regulate excitability of pyramidal neurons in distinct brain regions

  2017cites this paper
• Dopamine Pumping Up Spinal Locomotor Network Function

  2017cites this paper
• The neural control of heartbeat in invertebrates.

  2016cites this paper