Related Experiment Video
Updated: Jun 12, 2026

Contribution of the Na+/K+ Pump to Rhythmic Bursting, Explored with Modeling and Dynamic Clamp Analyses
Published on: May 9, 2021
Pacemaking in dopaminergic ventral tegmental area neurons: depolarizing drive from background and voltage-dependent
1Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA. zayd_khaliq@hms.harvard.edu
Abstract:
Dopaminergic neurons in the ventral tegmental area (VTA) fire spontaneously in a pacemaker-like manner. We analyzed the ionic currents that drive pacemaking in dopaminergic VTA neurons, studied in mouse brain slices. Pacemaking was not inhibited by blocking hyperpolarization-activated cation current (I(h)) or blocking all calcium current by Mg(2+) replacement of Ca(2+). Tetrodotoxin (TTX) stopped spontaneous activity and usually resulted in stable resting potentials near -60 mV to -55 mV, 10-15 mV below the action potential threshold. When external sodium was replaced by N-methyl-D-glucamine (NMDG) with TTX present, cells hyperpolarized by an average of -11 mV, suggesting a significant resting sodium conductance not sensitive to TTX. Voltage-clamp experiments using slow (10 mV/s) ramps showed a steady-state, steeply voltage-dependent current blocked by TTX that activates near -60 mV, as well as a sodium "background" current with little voltage sensitivity, revealed by NMDG replacement for sodium with TTX present. We quantified these two components of sodium current during the pacemaking trajectory using action potential clamp. The initial phase of depolarization, up to approximately -55 mV, is driven mainly by non-voltage-dependent sodium background current. Above -55 mV, TTX-sensitive voltage-dependent "persistent" Na current helps drive the final phase of depolarization to the spike threshold. Voltage-dependent calcium current is small at all subthreshold voltages. The pacemaking mechanism in VTA neurons differs from that in substantia nigra pars compacta (SNc) neurons, where subthreshold calcium current plays a dominant role. In addition, we found that non-voltage-dependent background sodium current is much smaller in SNc neurons than VTA neurons.
Related Concept Videos
Action Potentials
Action Potential
Membrane potential in neurons
Neurons typically have a resting membrane potential of about -70 millivolts (mV). When they receive...
Action Potential
Membrane potential in neurons
Neurons typically have a resting membrane potential of about -70 millivolts (mV). When they receive...
Action Potential: Phases of Stimulation
Resting Phase:
In this phase, the cell's membrane is at its resting potential, typically around -70 millivolts (mV) for neurons. Inside the cell, there is a higher concentration of potassium ions (K+) and a lower concentration of sodium ions (Na+). Voltage-gated sodium channels are closed, and...
The Role of Ion Channels in Neuronal Computation
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential.
Propagation of Action Potentials
Neurons (nerve cells) have a resting membrane potential, with a slightly negative charge inside compared to outside. This is maintained by ion channels, such as sodium (Na+) and potassium (K+) channels, which control the flow of ions. When a stimulus, like a touch or a signal from another neuron, triggers the neuron, sodium channels open, allowing sodium ions to...

