A Computer Model of the Electrocardiogram Based on Cellular Action Potentials in a Bidomain Model of the Myocardium

Dendrotoxin blocks accommodation in frog myelinated axons

Journal of Neurophysiology ◽

10.1152/jn.1989.62.1.174 ◽

1989 ◽

Vol 62 (1) ◽

pp. 174-184 ◽

Cited By ~ 14

Author(s):

M. O. Poulter ◽

T. Hashiguchi ◽

A. L. Padjen

Keyword(s):

Action Potential ◽

Computer Model ◽

Action Potentials ◽

Potassium Conductance ◽

Constant Stimulus ◽

Motor Axons ◽

Myelinated Axons ◽

Frequency Adaptation ◽

Potassium Conductances ◽

Slow Potassium

1. Intracellular microelectrode recordings from large sensory and motor myelinated axons in spinal roots of Rana pipiens were used to study the effects of dendrotoxin (DTX), a specific blocker of a fast activating potassium current (GKf1). 2. Dendrotoxin reduced the ability of myelinated sensory and motor axons to accommodate to a constant stimulus. A depolarizing current step, which normally evoked only one action potential, after dendrotoxin treatment (200-500 nM) produced a train of action potentials. These spike trains lasted 29 +/- 2.8 (SE) ms on average in sensory fibers (n = 18) and 40.2 +/- 4.5 ms in motor fibers (n = 9). 3. After dendrotoxin treatment, in addition to a reduction in the ability to accommodate to a constant stimulus, a slowing in the rate of action potential generation was evident (spike frequency adaptation). 4. Dendrotoxin had no effect on the rising phase of conducted action potentials evoked by peripheral stimulation. Together with a lack of effect on the absolute refractory period, these results indicate that dendrotoxin does not affect sodium channel activity. 5. The steady-state voltage/current relationship was unchanged in response to hyperpolarizing current pulses; however, there was a significant increase in cord resistance in response to depolarizing current steps, demonstrating that DTX decreases outward rectification. 6. A computer model based on Hodgkin and Huxley equations was developed, which included the three voltage-dependent potassium conductances described by Dubois. The model reproduced major experimental results: removal of the conductance, termed GKf1, reduced the accommodation in the early phase of a continuous stimulus, indicating that this current could be responsible for the early accommodation. The hypothesis that the slow potassium conductance GKs regulates late accommodation and action potential frequency adaptation is also supported by the computer model. 7. In summary, these results suggest that in amphibian myelinated sensory and motor axons, the activity of potassium conductances can account for accommodation and adaptation without involvement of sodium conductance activity.

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Modeling of lamprey reticulospinal neurons: multiple distinct parameter sets yield realistic simulations

Journal of Neurophysiology ◽

10.1152/jn.00070.2020 ◽

2020 ◽

Vol 124 (3) ◽

pp. 895-913

Author(s):

Jeffrey A. Ruffolo ◽

Andrew D. McClellan

Keyword(s):

Ion Channels ◽

Parameter Space ◽

Computer Model ◽

Action Potentials ◽

Search Algorithm ◽

Repetitive Firing ◽

Reticulospinal Neurons

A computer model of lamprey reticulospinal neurons with a default parameter set produced simulations of action potentials and repetitive firing that scored favorably compared with the properties of these neurons. A dual-annealing search algorithm explored ~50 million parameter sets and identified 4,302 distinct viable parameter sets within parameter space that yielded higher/much higher scores than the default parameter set. In addition, 5- and 2-conductance grid searches identified significant correlations between maximum conductances for pairs of ion channels.

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