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Action potential generation requires a high sodium channel density in the axon initial segment
Maarten H P Kole1, Susanne U Ilschner, Björn M Kampa
1Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Garran Road, Canberra ACT 0200, Australia.
Nature Neuroscience
|January 22, 2008
Summary
Action potentials require a high density of voltage-gated sodium channels at the axon initial segment (AIS). This density is maintained by anchoring to the actin cytoskeleton, resolving a long-standing paradox in neuroscience.
Area of Science:
- Neuroscience
- Cell Biology
- Computational Biology
Background:
- The axon initial segment (AIS) is critical for action potential initiation in neurons.
- High density of voltage-gated sodium channels was presumed necessary at the AIS.
- Previous patch-clamp studies indicated similar sodium channel densities in the AIS and soma.
Purpose of the Study:
- To resolve the discrepancy in measured sodium channel density at the AIS.
- To determine the actual sodium channel density at the AIS of cortical pyramidal neurons.
- To investigate the role of cytoskeletal anchoring in maintaining sodium channel density.
Main Methods:
- Antibody staining
- Whole-cell voltage-clamp recordings
- Sodium imaging
- Computational modeling
- Actin cytoskeleton disruption
Main Results:
- Sodium channel density at the AIS is approximately 50 times higher than in proximal dendrites.
- Disruption of the actin cytoskeleton increased measured sodium currents at the AIS.
- Computational models necessitate a high sodium channel density at the AIS for accurate action potential generation and backpropagation.
Conclusions:
- Action potential generation relies on a high density of sodium channels specifically at the AIS.
- The actin cytoskeleton plays a crucial role in anchoring sodium channels at the AIS.
- This anchoring mechanism explains the high functional sodium channel density at the AIS.
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01:41Action Potentials
Overview
01:28Action Potential: Phases of Stimulation
The action potential is a complex electrical event that occurs in excitable cells, such as neurons and muscle cells. It consists of several distinct phases, each with specific characteristics.
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...
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...
01:14Action Potential
Neurons communicate by firing action potentials—the electrochemical signal that is propagated along the axon. The signal results in the release of neurotransmitters at axon terminals, thereby transmitting information to the nervous system. An action potential is a specific "all-or-none" change in membrane potential that results in a rapid spike in voltage.
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Neurons communicate by firing action potentials—the electrochemical signal that is propagated along the axon. The signal results in the release of neurotransmitters at axon terminals, thereby transmitting information to the nervous system. An action potential is a specific "all-or-none" change in membrane potential that results in a rapid spike in voltage.
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01:24Generation of Action Potential in Skeletal Muscles
Every cell in the body maintains a membrane potential due to an uneven distribution of positive and negative charges across its plasma membrane. The membrane potential is measured in millivolts and quantifies the difference in charge across the membrane.
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01:23Propagation of Action Potentials
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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...