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

• Published in: eLife Vol. 5
• Main Authors: Kueh, Daniel, Barnett, William H, Cymbalyuk, Gennady S, Calabrese, Ronald L
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 02.09.2016; eLife Sciences Publications, Ltd
• Subjects: Action Potentials; Animals; Central pattern generator; Central Pattern Generators - physiology; Cesium - metabolism; Computational and Systems Biology; Equilibrium; Firing pattern; h-current; Heart; Hirudo medicinalis; Interneurons; Leeches; mathematical model; Monensin; Monensin - metabolism; Motor task performance; Na+/H+-exchanging ATPase; Na+/K+ pump; Na+/K+-exchanging ATPase; Neurogenesis; Neurons; Neuroscience; Ordinary differential equations; rhythmic activity; Sodium Ionophores - metabolism; Sodium-Hydrogen Exchangers - metabolism; Sodium-Potassium-Exchanging ATPase - metabolism; computational biology; systems biology; Na+/K+ pump; central pattern generator; Hirudo medicinalis; neuroscience; mathematical model; rhythmic activity; h-current
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.19322

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. In animals, cells called neurons relay information around the body in the form of electrical signals. An enzyme called the sodium and potassium pump is found in the membrane that surrounds neurons. It uses energy to pump sodium ions out of the neuron and potassium ions in the opposite direction. This helps to maintain different concentrations of these ions across the membrane, which is critical for the electrical activity of neurons and also generates an electrical current in the process. The size of the current is influenced by how many sodium ions have leaked back into the neuron due to the neuron’s electrical activity. Neurons control many rhythmic processes in animals including breathing and heartbeats. However, it was not clear how the current produced by the sodium and potassium pump contributes to the rhythms in neural activity that drive these processes. To address this question, Kueh et al. investigated the effect of drugs that alter the activity of the pump in neurons that control heartbeat in leeches. The experiments show that stimulating the pump by altering the amount of sodium ions that leak into the neuron dramatically sped up the rhythmic activity of these neurons. This effect depended completely on the presence of a channel protein – called an h-channel – that was activated with a delay by the altered pump current and allowed sodium and potassium ions to cross the membrane, counteracting the pump current. Inhibiting the pump also sped up the rhythm of neural activity, but this effect did not depend on the h-channel. Kueh et al. developed a computer model that indicated that the time course of the pump current following the sodium ion leak and the slow activation of the h-channel were important for these effects. Previous studies have shown that a particular signal molecule modulates the activity of both the pump and the h-channel in neurons. Therefore, a future challenge is to find out how the pump and the h-channel interact while their activities change in response to the signal molecule.