The role of ATP-sensitive potassium channels in a hippocampal neuron (Huang et al. 2007)
Project Description
"Hyperglycemia-related neuronal excitability and epileptic seizures
are not uncommon in clinical practice. However, their underlying
mechanism remains elusive. ATP-sensitive K(+) (K(ATP)) channels are
found in many excitable cells, including cardiac myocytes,
pancreatic beta cells, and neurons. These channels provide a link
between the electrical activity of cell membranes and cellular
metabolism. We investigated the effects of higher extracellular
glucose on hippocampal K(ATP) channel activities and neuronal
excitability. The cell-attached patch-clamp configuration on
cultured hippocampal cells and a novel multielectrode recording
system on hippocampal slices were employed. In addition, a
simulation modeling hippocampal CA3 pyramidal neurons (Pinsky-Rinzel
model) was analyzed to investigate the role of K(ATP) channels in
the firing of simulated action potentials. ..."
Sheng-Nan Wu
Chin-Wei Huang
This is the readme.txt for the model associated with the paper
Huang CW et al. Glucose and hippocampal neuronal excitability:
role of ATP-sensitive potassium channel. J Neurosci Res 2007,
[Epub ahead of print]
Abstract:
Hyperglycemia-related neuronal excitability and epileptic seizures
are not uncommon in clinical practice. However, their underlying
mechanism remains elusive. ATP-sensitive K(+) (K(ATP)) channels are
found in many excitable cells, including cardiac myocytes,
pancreatic beta cells, and neurons. These channels provide a link
between the electrical activity of cell membranes and cellular
metabolism. We investigated the effects of higher extracellular
glucose on hippocampal K(ATP) channel activities and neuronal
excitability. The cell-attached patch-clamp configuration on
cultured hippocampal cells and a novel multielectrode recording
system on hippocampal slices were employed. In addition, a
simulation modeling hippocampal CA3 pyramidal neurons (Pinsky-Rinzel
model) was analyzed to investigate the role of K(ATP) channels in
the firing of simulated action potentials. We found that incremental
extracellular glucose could attenuate the activities of hippocampal
K(ATP) channels. The effect was concentration dependent and involved
mainly in open probabilities, not single-channel conductance.
Additionally, higher levels of extracellular glucose could enhance
neuropropagation; this could be attenuated by diazoxide, a K(ATP)
channel agonist. In simulations, high levels of intracellular ATP,
used to mimic increased extracellular glucose or reduced conductance
of K(ATP) channels, enhanced the firing of action potentials in model
neurons. The stochastic increases in intracellular ATP levels also
demonstrated an irregular and clustered neuronal firing pattern. This
phenomenon of K(ATP) channel attenuation could be one of the underlying
mechanisms of glucose-related neuronal hyperexcitability and propagation.
To run the models:
XPP: start with the command
xpp ode\NeuronKATP_Stoch.ode
select Initialconds -> Go
This simulation will make graphs similar to figure 6A in the paper
or Neuron_Figure.jpg:
Drs. Sheng-Nan Wu and Ching-Wei Huang
National Cheng Kung University Medical Center
Tainan 70101, Taiwan
snwu@mail.ncku.edu.tw
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metadata.rdf
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Neuron_Figure.JPG
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NeuronKATP_Stoch.ode
XPP
NeuronKATP_Stoch.sedml
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