Target type: biologicalprocess
Any process that regulates the potential at which an axon potential is triggered. [ISBN:978-0071390118]
The firing threshold of an action potential is the minimum level of membrane depolarization required to trigger an action potential. This threshold is not a fixed value but rather a dynamic process that can be modulated by various factors, including the presence of neurotransmitters, neuromodulators, and changes in the membrane's electrical properties. Here is a detailed description of the biological processes involved in regulating action potential firing threshold:
**1. Ion Channel Activity:**
- **Sodium Channels:** Voltage-gated sodium channels are crucial for the initiation and propagation of action potentials. Their activation leads to a rapid influx of sodium ions, causing membrane depolarization. Changes in the opening and closing dynamics of sodium channels can influence the firing threshold. For instance, increased sodium channel conductance can lower the threshold, making it easier to generate an action potential.
- **Potassium Channels:** Voltage-gated potassium channels contribute to repolarization after an action potential. Their activation allows potassium ions to flow out of the neuron, restoring the resting membrane potential. The kinetics of potassium channel activation and inactivation can also impact the firing threshold. Delayed potassium channel opening can lead to a prolonged depolarized state, reducing the threshold and increasing excitability.
**2. Synaptic Input:**
- **Excitatory Neurotransmitters:** Neurotransmitters like glutamate, acetylcholine, and dopamine typically cause depolarization of the postsynaptic neuron by increasing sodium permeability or activating other excitatory ion channels. This depolarization can bring the membrane potential closer to the firing threshold, making it more likely to generate an action potential.
- **Inhibitory Neurotransmitters:** Neurotransmitters like GABA and glycine hyperpolarize the postsynaptic neuron by increasing chloride permeability or activating other inhibitory ion channels. This hyperpolarization pushes the membrane potential further away from the firing threshold, reducing neuronal excitability and making it less likely to generate an action potential.
**3. Membrane Properties:**
- **Membrane Resistance:** The resistance of the neuronal membrane to ion flow can affect the firing threshold. Higher membrane resistance will make it harder for depolarizing currents to spread, increasing the threshold. Conversely, lower membrane resistance will facilitate depolarization and decrease the threshold.
- **Capacitance:** Membrane capacitance reflects the ability of the membrane to store electrical charge. A higher capacitance will require more charge to depolarize the membrane to threshold, thus increasing the firing threshold.
**4. Neuronal Modulators:**
- **Second Messenger Systems:** Various intracellular signaling pathways, triggered by neurotransmitters or other stimuli, can modify the firing threshold by altering the expression or phosphorylation state of ion channels. For example, cAMP-dependent protein kinase (PKA) can phosphorylate and activate certain ion channels, leading to changes in membrane excitability and firing threshold.
- **Long-term Potentiation (LTP) and Long-term Depression (LTD):** These processes, associated with synaptic plasticity, involve long-lasting changes in synaptic strength that can modify the firing threshold. LTP typically increases synaptic efficacy, lowering the threshold, while LTD decreases synaptic efficacy, raising the threshold.
**5. Intrinsic Properties:**
- **Resting Membrane Potential:** The resting membrane potential sets the baseline for neuronal excitability. A more negative resting membrane potential will require more depolarization to reach threshold, increasing the firing threshold.
- **Refractory Period:** After an action potential, neurons enter a refractory period during which they are less excitable. The absolute refractory period is characterized by complete inability to generate another action potential, while the relative refractory period requires a stronger stimulus to trigger an action potential. The duration of the refractory period can influence the frequency of action potential firing.
**6. Environmental Factors:**
- **Temperature:** Temperature affects the kinetics of ion channels, influencing the firing threshold. Higher temperatures can accelerate channel opening and closing, potentially lowering the threshold.
- **pH:** Changes in pH can alter the activity of ion channels and other membrane proteins, influencing the firing threshold.
**In conclusion, the regulation of action potential firing threshold is a complex process involving numerous factors that interact at multiple levels, including ion channel activity, synaptic input, membrane properties, neuronal modulators, intrinsic properties, and environmental influences.**'"
Protein | Definition | Taxonomy |
---|---|---|
Potassium voltage-gated channel subfamily KQT member 3 | A voltage-gated potassium channel subunit KCNQ3 that is encoded in the genome of human. [] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
N-(2-aminoethyl)-5-chloro-1-naphthalenesulfonamide | naphthalenes; sulfonic acid derivative | ||
flupirtine | flupirtine: RN given refers to parent cpd without isomeric designation | aminopyridine | |
ezogabine | ezogabine : A substituted aniline that is benzene-1,2,4-triamine bearing ethoxycarbonyl and 4-fluorobenzyl substituents at positions N-1 and N-4 respectively. An anticonvulsant used to treat seizures associated with epilepsy in adults. ezogabine: structure in first source | carbamate ester; organofluorine compound; secondary amino compound; substituted aniline | anticonvulsant; potassium channel modulator |
bms204352 | BMS204352: a calcium-sensitive opener of maxi-K potassium channels; structure in first source | ||
N-(2,4,6-trimethylphenyl)-3-bicyclo[2.2.1]heptanecarboxamide | monoterpenoid | ||
n-(6-chloropyridin-3-yl)-4-fluorobenzamide | N-(6-chloropyridin-3-yl)-4-fluorobenzamide: structure in first source | ||
ica 27243 | N-(6-Chloropyridin-3-yl)-3,4-difluorobenzamide: a KCNQ2/3 channel activator; structure in first source | ||
a 803467 | A 803467: an Nav1.8 sodium channel blocker; structure in first source |