COMPUTATIONAL STUDY OF THE EFFECTS OF THE Ether-a-go-go-related GENE POTASSIUM CURRENT IN MODULATING SPONTANEOUS ACTIVITY OF DOPAMINERGIC NEURONS
Document Type
Presentation
Start Date
22-10-2010 10:45 AM
End Date
22-10-2010 12:00 PM
Description
The purpose of the present study is to investigate; using computational and mathematical methods, the effects of the Ether-a-go-go-related gene (ERG) K current in the dynamics of dopaminergic (DA) neurons, both under electrical or synaptic stimulation and during spontaneous activity. Presently, experimental evidence indicates a 50% increase in the spiking frequency of spontaneously active dopaminergic neurons after bath application of the HERG blocker E-4031 or the HERG toxin BeKm-1. To investigate this effect, we perform numerical experiments on a compartmental DA neuron model comprised of one somatic, four proximal and eight distal dendritic compartments (cf. Kuznetsova et al. J Comput. Neurosci. 2010). Membrane potential in each compartment is computed from an equivalent circuit that contains a mathematical description of relevant membrane currents found in DA neurons. Additionally, compartmental changes in Ca2+ and Na+ concentrations are also computed from these currents and non-and electrogenic Ca2+ and Na+ pumps. The description of the ERG current is taken from Canavier et al. 2007, with parameters adjusted to reproduce voltage clamp experiments on HERG channels expressed in Xenopus oocytes (Ficker et al 1998). Results indicate that, due to the particular gating property of the HERG current, where inactivation is faster than activation, ERG channels quickly inactivate during an action potential. However, during the afterhyperpolarization, ERG channels move back from their inactivated state into the open state and then slowly go into the closed state until the next action potential. This long-lasting decay of the open state increases the interspike interval (ISi). Consequently, blockage of the ERG channel leads to a shortening of the ISi, in agreement with the experimental evidence indicated above.
Recommended Citation
Huertas, Marco Antonio and Canavier, C. C., "COMPUTATIONAL STUDY OF THE EFFECTS OF THE Ether-a-go-go-related GENE POTASSIUM CURRENT IN MODULATING SPONTANEOUS ACTIVITY OF DOPAMINERGIC NEURONS" (2010). Dr. Joseph M. Moerschbaecher, III Graduate Research Day. 10.
https://digitalscholar.lsuhsc.edu/grad_rs/2010/poster1/10
COMPUTATIONAL STUDY OF THE EFFECTS OF THE Ether-a-go-go-related GENE POTASSIUM CURRENT IN MODULATING SPONTANEOUS ACTIVITY OF DOPAMINERGIC NEURONS
The purpose of the present study is to investigate; using computational and mathematical methods, the effects of the Ether-a-go-go-related gene (ERG) K current in the dynamics of dopaminergic (DA) neurons, both under electrical or synaptic stimulation and during spontaneous activity. Presently, experimental evidence indicates a 50% increase in the spiking frequency of spontaneously active dopaminergic neurons after bath application of the HERG blocker E-4031 or the HERG toxin BeKm-1. To investigate this effect, we perform numerical experiments on a compartmental DA neuron model comprised of one somatic, four proximal and eight distal dendritic compartments (cf. Kuznetsova et al. J Comput. Neurosci. 2010). Membrane potential in each compartment is computed from an equivalent circuit that contains a mathematical description of relevant membrane currents found in DA neurons. Additionally, compartmental changes in Ca2+ and Na+ concentrations are also computed from these currents and non-and electrogenic Ca2+ and Na+ pumps. The description of the ERG current is taken from Canavier et al. 2007, with parameters adjusted to reproduce voltage clamp experiments on HERG channels expressed in Xenopus oocytes (Ficker et al 1998). Results indicate that, due to the particular gating property of the HERG current, where inactivation is faster than activation, ERG channels quickly inactivate during an action potential. However, during the afterhyperpolarization, ERG channels move back from their inactivated state into the open state and then slowly go into the closed state until the next action potential. This long-lasting decay of the open state increases the interspike interval (ISi). Consequently, blockage of the ERG channel leads to a shortening of the ISi, in agreement with the experimental evidence indicated above.