Target type: cellularcomponent
Portion of the axon proximal to the neuronal cell body, at the level of the axon hillock. The action potentials that propagate along the axon are generated at the level of this initial segment. [GOC:nln, GOC:sl, PMID:1754851, PMID:21551097]
The axon initial segment (AIS) is a specialized membrane domain located at the proximal axon, where action potentials are initiated. It is characterized by a unique molecular composition, including a high density of voltage-gated sodium channels, which are essential for action potential generation. The AIS also contains a variety of other proteins, such as ion channels, scaffolding proteins, and signaling molecules, which contribute to its unique function. The cytoskeleton of the AIS is composed of a dense network of microtubules, actin filaments, and intermediate filaments, which provide structural support and regulate the localization and function of AIS proteins. The AIS is a dynamic structure that can be remodeled in response to changes in neuronal activity or injury. This plasticity is important for maintaining proper neuronal function and plasticity. The cellular component of the AIS can be further broken down into several sub-components, including the following:
1. **Plasma membrane:** The plasma membrane of the AIS is enriched in voltage-gated sodium channels, which are responsible for the rapid depolarization that initiates action potentials. Other important membrane proteins include potassium channels, which help to repolarize the membrane after an action potential, and calcium channels, which are involved in synaptic transmission.
2. **Cytoskeleton:** The cytoskeleton of the AIS provides structural support and helps to organize the distribution of AIS proteins. The major cytoskeletal components include microtubules, which are involved in the transport of proteins and organelles, actin filaments, which are involved in the regulation of membrane dynamics, and intermediate filaments, which provide mechanical strength.
3. **Adhesive junctions:** The AIS is connected to the cell body and the axon by specialized adhesive junctions, which help to maintain the structural integrity of the AIS and facilitate communication between these compartments. These junctions are composed of proteins that interact with the cytoskeleton and the plasma membrane, providing a stable and functional link between the different cellular domains.
4. **Signaling molecules:** The AIS is a site of intense signaling activity, with a variety of signaling molecules being involved in regulating its function. These molecules include kinases, phosphatases, and second messengers, which play a role in modulating the activity of AIS proteins, such as ion channels and scaffolding proteins.
5. **Organelles:** The AIS contains a variety of organelles, including mitochondria, which provide energy for the AIS, endoplasmic reticulum, which is involved in protein synthesis and folding, and Golgi apparatus, which processes and packages proteins for transport.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Sodium channel protein type 8 subunit alpha | A sodium channel protein type 8 subunit alpha that is encoded in the genome of human. [PRO:WCB, UniProtKB:Q9UQD0] | Homo sapiens (human) |
| Potassium voltage-gated channel subfamily A member 1 | A voltage-gated potassium channel subunit KCNA1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q09470] | Homo sapiens (human) |
| Sodium channel protein type 1 subunit alpha | A sodium channel protein type 1 subunit alpha that is encoded in the genome of human. [PRO:WCB, UniProtKB:P35498] | Homo sapiens (human) |
| Potassium voltage-gated channel subfamily A member 4 | A voltage-gated potassium channel alpha subunit KCNA4 that is encoded in the genome of human. [] | Homo sapiens (human) |
| Potassium voltage-gated channel subfamily A member 2 | A voltage-gated potassium channel subunit KCNA2 that is encoded in the genome of human. [] | Homo sapiens (human) |
| Potassium voltage-gated channel subfamily KQT member 2 | A voltage-gated potassium channel subunit KCNQ2 that is encoded in the genome of human. [] | Homo sapiens (human) |
| 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 |
|---|---|---|---|
| 4-aminopyridine | aminopyridine; aromatic amine | avicide; orphan drug; potassium channel blocker | |
| phenytoin | imidazolidine-2,4-dione | anticonvulsant; drug allergen; sodium channel blocker; teratogenic agent | |
| N-(2-aminoethyl)-5-chloro-1-naphthalenesulfonamide | naphthalenes; sulfonic acid derivative | ||
| amiodarone | amiodarone : A member of the class of 1-benzofurans that is 1-benzofuran substituted by a butyl group at position 2 and a 4-[2-(diethylamino)ethoxy]-3,5-diiodobenzoyl group at position 3. It is a cardiovascular drug used for the treatment of cardiac dysrhythmias. Amiodarone: An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance. | 1-benzofurans; aromatic ketone; organoiodine compound; tertiary amino compound | cardiovascular drug |
| amitriptyline | amitriptyline : An organic tricyclic compound that is 10,11-dihydro-5H-dibenzo[a,d][7]annulene substituted by a 3-(dimethylamino)propylidene group at position 5. Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antagonize cholinergic and alpha-1 adrenergic responses to bioactive amines. | carbotricyclic compound; tertiary amine | adrenergic uptake inhibitor; antidepressant; environmental contaminant; tropomyosin-related kinase B receptor agonist; xenobiotic |
| 5-methoxypsoralen | 5-methoxypsoralen : A 5-methoxyfurocoumarin that is psoralen substituted by a methoxy group at position 5. 5-Methoxypsoralen: A linear furanocoumarin that has phototoxic and anti-inflammatory properties, with effects similar to METHOXSALEN. It is used in PUVA THERAPY for the treatment of PSORIASIS. | 5-methoxyfurocoumarin; organic heterotricyclic compound; psoralens | hepatoprotective agent; plant metabolite |
| chlorpromazine | chlorpromazine : A substituted phenothiazine in which the ring nitrogen at position 10 is attached to C-3 of an N,N-dimethylpropanamine moiety. Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking DOPAMINE RECEPTORS. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. | organochlorine compound; phenothiazines; tertiary amine | anticoronaviral agent; antiemetic; dopaminergic antagonist; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor; phenothiazine antipsychotic drug |
| cifenline | diarylmethane | ||
| flecainide | flecainide : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 2,5-bis(2,2,2-trifluoroethoxy)benzoic acid with the primary amino group of piperidin-2-ylmethylamine. An antiarrhythmic agent used (in the form of its acetate salt) to prevent and treat tachyarrhythmia (abnormal fast rhythm of the heart). Flecainide: A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial ARRHYTHMIAS and TACHYCARDIAS. | aromatic ether; monocarboxylic acid amide; organofluorine compound; piperidines | anti-arrhythmia drug |
| haloperidol | haloperidol : A compound composed of a central piperidine structure with hydroxy and p-chlorophenyl substituents at position 4 and an N-linked p-fluorobutyrophenone moiety. Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279) | aromatic ketone; hydroxypiperidine; monochlorobenzenes; organofluorine compound; tertiary alcohol | antidyskinesia agent; antiemetic; dopaminergic antagonist; first generation antipsychotic; serotonergic antagonist |
| imipramine | imipramine : A dibenzoazepine that is 5H-dibenzo[b,f]azepine substituted by a 3-(dimethylamino)propyl group at the nitrogen atom. Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. | dibenzoazepine | adrenergic uptake inhibitor; antidepressant; EC 3.4.21.26 (prolyl oligopeptidase) inhibitor |
| mexiletine | mexiletine : An aromatic ether which is 2,6-dimethylphenyl ether of 2-aminopropan-1-ol. Mexiletine: Antiarrhythmic agent pharmacologically similar to LIDOCAINE. It may have some anticonvulsant properties. | aromatic ether; primary amino compound | anti-arrhythmia drug |
| nifedipine | Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. | C-nitro compound; dihydropyridine; methyl ester | calcium channel blocker; human metabolite; tocolytic agent; vasodilator agent |
| nitrendipine | nitrendipine : A dihydropyridine that is 1,4-dihydropyridine substituted by methyl groups at positions 2 and 6, a 3-nitrophenyl group at position 4, a ethoxycarbonyl group at position 3 and a methoxycarbonyl group at position 5. It is a calcium-channel blocker used in the treatment of hypertension. Nitrendipine: A calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive. | C-nitro compound; dicarboxylic acids and O-substituted derivatives; diester; dihydropyridine; ethyl ester; methyl ester | antihypertensive agent; calcium channel blocker; geroprotector; vasodilator agent |
| phenobarbital | phenobarbital : A member of the class of barbiturates, the structure of which is that of barbituric acid substituted at C-5 by ethyl and phenyl groups. Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. | barbiturates | anticonvulsant; drug allergen; excitatory amino acid antagonist; sedative |
| tetracaine | tetracaine : A benzoate ester in which 4-N-butylbenzoic acid and 2-(dimethylamino)ethanol have combined to form the ester bond; a local ester anaesthetic (ester caine) used for surface and spinal anaesthesia. Tetracaine: A potent local anesthetic of the ester type used for surface and spinal anesthesia. | benzoate ester; tertiary amino compound | local anaesthetic |
| tetraethylammonium | Tetraethylammonium: A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90) | quaternary ammonium ion | |
| naphthazarin | naphthazarin : A naphthoquinone that is 1,4-naphthoquinone in which the hydrogens at positions 5 and 8 are replaced by hydroxy groups. naphthazarin: fish toxin; isolated for first time from the walnut onigurmi, Juglans mandshurica maxim var. Sieboldiana Makino; structure | hydroxy-1,4-naphthoquinone | acaricide; antibacterial agent; antineoplastic agent; apoptosis inducer; geroprotector; plant metabolite |
| pimozide | pimozide : A member of the class of benzimidazoles that is 1,3-dihydro-2H-benzimidazol-2-one in which one of the nitrogens is substituted by a piperidin-4-yl group, which in turn is substituted on the nitrogen by a 4,4-bis(p-fluorophenyl)butyl group. Pimozide: A diphenylbutylpiperidine that is effective as an antipsychotic agent and as an alternative to HALOPERIDOL for the suppression of vocal and motor tics in patients with Tourette syndrome. Although the precise mechanism of action is unknown, blockade of postsynaptic dopamine receptors has been postulated. (From AMA Drug Evaluations Annual, 1994, p403) | benzimidazoles; heteroarylpiperidine; organofluorine compound | antidyskinesia agent; dopaminergic antagonist; first generation antipsychotic; H1-receptor antagonist; serotonergic antagonist |
| mexiletine hydrochloride | mexiletine hydrochloride : A hydrochloride composed of equimolar amounts of mexiletine and hydrogen chloride. | hydrochloride | anti-arrhythmia drug |
| diltiazem | diltiazem : A 5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl acetate in which both stereocentres have S configuration. A calcium-channel blocker and vasodilator, it is used as the hydrochloride in the management of angina pectoris and hypertension. Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions. | 5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-3-yl acetate | antihypertensive agent; calcium channel blocker; vasodilator agent |
| flupirtine | flupirtine: RN given refers to parent cpd without isomeric designation | aminopyridine | |
| sertindole | sertindole : A phenylindole that is 1H-indole which is substituted on the nitrogen by a p-chlorophenyl group, at position 5 by chlorine, and at position 3 by a piperidin-4-yl group, which is itself substituted on the nitrogen by a 2-(2-oxoimidazolidin-1-yl)ethyl group. | heteroarylpiperidine; imidazolidinone; organochlorine compound; organofluorine compound; phenylindole | alpha-adrenergic antagonist; H1-receptor antagonist; second generation antipsychotic; serotonergic antagonist |
| mibefradil | Mibefradil: A benzimidazoyl-substituted tetraline that selectively binds and inhibits CALCIUM CHANNELS, T-TYPE. | tetralins | T-type calcium channel blocker |
| tedisamil | tedisamil : A member of the class of diazabicyclononanes that is (1s,5s)-3,7-diazaspiro[bicyclo[3.3.1]nonane-9,1'-cyclopentane] in which the hydrogens at positions 3 and 7 are replaced by cyclopropylmethyl groups. It is a potassium channel blocker and an antiarrhythmic agent currently currently in development for the treatment of atrial fibrillation. | ||
| uk 68798 | aromatic ether; sulfonamide; tertiary amino compound | anti-arrhythmia drug; potassium channel blocker | |
| 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 |
| n-methylpiperidin-4-yl propionate | |||
| cns 5161 | CNS 5161: structure in first source | ||
| bms204352 | BMS204352: a calcium-sensitive opener of maxi-K potassium channels; structure in first source | ||
| senicapoc | senicapoc: a Gardos channel blocker; structure in first source | ||
| cortisone | 11-oxo steroid; 17alpha-hydroxy steroid; 20-oxo steroid; 21-hydroxy steroid; 3-oxo-Delta(4) steroid; C21-steroid; glucocorticoid; primary alpha-hydroxy ketone; tertiary alpha-hydroxy ketone | human metabolite; mouse metabolite | |
| xe 991, anthracenone | 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone: neurotransmitter release enhancer and potassium channel blocker; structure given in first source | anthracenes | |
| ica-121431 | ICA-121431: structure in first source | ||
| capsaicin | ALGRX-4975: an injectable capsaicin (TRPV1 receptor agonist) formulation for longlasting pain relief capsaicinoid : A family of aromatic fatty amides produced as secondary metabolites by chilli peppers. | capsaicinoid | non-narcotic analgesic; TRPV1 agonist; voltage-gated sodium channel blocker |
| 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 | ||
| clathrodin | clathrodin: structure given in first source; isolated from marine sponges of the genus Agelas | ||
| oroidin | oroidin: from marine sponges of the genus Agelas; structure in first source | pyrroles; secondary carboxamide | metabolite |
| hymenidin | hymenidin: serotonergic receptor antagonist from Okinawan marine sponge Hymeniacidon; structure given in first source | ||
| 2-ethyl-5-methoxy-n,n-dimethyltryptamine | 2-ethyl-5-methoxy-N,N-dimethyltryptamine: a 5-HT(6) receptor agonist; structure in first source | ||
| 10,10-bis((2-fluoro-4-pyridinyl)methyl)-9(10h)-anthracenone | DMP 543: neurotransmitter release enhancer; structure given in first source | anthracenes | |
| ica 27243 | N-(6-Chloropyridin-3-yl)-3,4-difluorobenzamide: a KCNQ2/3 channel activator; structure in first source | ||
| 5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1h-indole | 5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole: a 5-HT6 agonist; structure in first source | indoles | |
| tetrodotoxin | |||
| a 803467 | A 803467: an Nav1.8 sodium channel blocker; structure in first source | ||
| cnv1014802 | vixotrigine: a sodium channel blocker | ||
| (r)-n-(4-(4-methoxyphenyl)thiazol-2-yl)-1-tosylpiperidine-2-carboxamide | (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1-tosylpiperidine-2-carboxamide: structure in first source | ||
| saxitoxin | saxitoxin : An alkaloid isolated from the marine dinoflagellates and cyanobacteria that causes paralytic shellfish poisoning. Saxitoxin: A compound that contains a reduced purine ring system but is not biosynthetically related to the purine alkaloids. It is a poison found in certain edible mollusks at certain times; elaborated by GONYAULAX and consumed by mollusks, fishes, etc. without ill effects. It is neurotoxic and causes RESPIRATORY PARALYSIS and other effects in MAMMALS, known as paralytic SHELLFISH poisoning. | alkaloid; carbamate ester; guanidines; ketone hydrate; paralytic shellfish toxin; pyrrolopurine | cyanotoxin; marine metabolite; neurotoxin; sodium channel blocker; toxin |
| gs-458967 | 6-(4-(trifluoromethoxy)phenyl)-3-(trifluoromethyl)(1,2,4)triazolo(4,3-a)pyridine: an anti-arrhythmia agent that inhibits late sodium current; structure in first source | ||
| ajmaline |