Ion Channels & Membrane Physiology
Ion Channels & Membrane Physiology
What Do You Need to Know?
- Electrolyte gradients — intracellular vs extracellular concentrations of Na+, K+, Ca2+, Cl−; Nernst equation gives equilibrium potential for each ion; Goldman equation determines resting membrane potential
- Resting membrane potential — approximately −70 mV, set primarily by K+ leak channels; Na+/K+ ATPase is electrogenic (3 Na+ out, 2 K+ in)
- Ion channel types — voltage-gated (Na+, K+, Ca2+), ligand-gated (nAChR, NMDA, AMPA, GABA-A, glycine), mechanically-gated, leak channels; alpha subunit = pore-forming
- Nav channel subtypes — Nav1.1–Nav1.9 with distinct tissue distributions and channelopathies (SCN1A = Dravet, GEFS+); blocked by TTX, local anesthetics, antiepileptics
- Calcium channel subtypes — L/N/P-Q/R/T types; P/Q antibodies = Lambert-Eaton; T-type = absence seizures (ethosuximide)
- Channelopathies — periodic paralysis, episodic ataxias, myotonias, epilepsies; know gene-channel-phenotype associations
- Drugs targeting ion channels — antiepileptics, local anesthetics, toxins, and their specific channel targets
Electrolyte Concentrations & Membrane Equations
Intracellular vs Extracellular Ion Concentrations
| Ion | Intracellular (mM) | Extracellular (mM) | Equilibrium Potential (Eion) | Direction at Rest |
|---|---|---|---|---|
| K+ | ~140 | ~4 | −90 mV | Outward (down concentration gradient) |
| Na+ | ~15 | ~145 | +60 mV | Inward |
| Ca2+ | ~0.0001 | ~2 | +120 mV | Inward |
| Mg2+ | ~0.5 | ~1 | — | Variable; blocks NMDA channel at rest |
| Cl− | ~5–15 | ~110 | −70 to −80 mV | Inward (in most adult neurons) |
| HCO3− | ~12 | ~24 | −33 mV | Outward through GABA-A channels |
Nernst Equation
- Purpose: calculates the equilibrium (reversal) potential for a single ion
- Formula: Eion = (RT/zF) × ln([ion]out / [ion]in)
- At 37°C, simplified: Eion = (61.5/z) × log10([ion]out / [ion]in)
- Equilibrium potential = voltage at which there is no net movement of that ion
Goldman-Hodgkin-Katz (GHK) Equation
- Purpose: determines the resting membrane potential considering the relative permeability to multiple ions
- Accounts for Na+, K+, and Cl− with their respective permeabilities (P)
- At rest, PK >> PNa (~40:1) → resting potential is closest to EK
- During an action potential, PNa briefly exceeds PK → membrane approaches ENa
Board Pearl
The resting membrane potential (−70 mV) is closest to EK (−90 mV) because K+ permeability dominates at rest. It is not exactly EK because of small Na+ leak inward. Hyperkalemia depolarizes the resting membrane → initial hyperexcitability, then inexcitability (depolarization block).
Resting Membrane Potential
Key Determinants
- K+ leak channels (two-pore domain, K2P) — primary determinant; open at rest, allowing K+ efflux
- Na+/K+ ATPase — pumps 3 Na+ out and 2 K+ in per cycle = net loss of 1 positive charge = electrogenic (contributes ~−5 to −10 mV)
- Concentration gradients — maintained by Na+/K+ ATPase; if pump fails (ischemia, digoxin toxicity) → gradients dissipate → depolarization
Na+/K+ ATPase
| Feature | Detail |
|---|---|
| Stoichiometry | 3 Na+ out, 2 K+ in per ATP hydrolyzed |
| Net effect | Electrogenic — hyperpolarizes membrane by ~5–10 mV |
| Energy cost | Consumes ~40–70% of brain's ATP |
| Inhibitors | Digoxin, ouabain (cardiac glycosides) — bind alpha subunit |
| Clinical | Ischemia → ATP depletion → pump failure → K+ accumulates extracellularly, Na+ accumulates intracellularly → depolarization → excitotoxicity |
Board Pearl
Do not confuse electrogenic with the primary determinant of resting potential. The Na+/K+ ATPase is electrogenic (contributes ~−5 to −10 mV), but the resting membrane potential is primarily set by K+ leak channels and the K+ concentration gradient the pump maintains.
Ion Channel Types — Classification
Overview by Gating Mechanism
| Channel Type | Gating Signal | Examples | Key Features |
|---|---|---|---|
| Voltage-gated | Change in membrane potential | Nav (Na+), Kv (K+), Cav (Ca2+) | Action potentials, repolarization, neurotransmitter release |
| Ligand-gated (ionotropic) | Neurotransmitter binding | nAChR, NMDA, AMPA, GABA-A, Glycine, 5-HT3 | Fast synaptic transmission (EPSPs and IPSPs) |
| Mechanically-gated | Mechanical deformation | Piezo1, Piezo2, hair cell channels | Touch, proprioception, hearing, baroreception |
| Leak (constitutively open) | Always open | K2P (two-pore K+ channels), some Na+ leak | Set resting membrane potential |
Ion Channel Structure
- Alpha (α) subunit — pore-forming subunit; determines ion selectivity and gating properties; target of most channel-blocking drugs and toxins
- Beta (β) and auxiliary subunits — modulatory; regulate trafficking, gating kinetics, and surface expression
- Voltage-gated Na+ and Ca2+ channels: single alpha subunit with 4 homologous domains (I–IV), each with 6 transmembrane segments (S1–S6); S4 = voltage sensor
- Voltage-gated K+ channels: 4 separate alpha subunits assemble as a tetramer
- Ligand-gated channels: typically pentameric (nAChR, GABA-A, glycine, 5-HT3) or tetrameric (NMDA, AMPA, kainate)
Voltage-Gated Sodium Channels (Nav)
Activation and Inactivation Gates
- Activation gate (m gate) — opens rapidly upon depolarization → Na+ influx → rising phase of action potential
- Inactivation gate (h gate) — closes within ~1 ms after activation → terminates Na+ influx; responsible for the absolute refractory period
- Three channel states: resting (closed but ready), open (activated), inactivated (closed, cannot reopen until repolarization)
- Recovery from inactivation requires membrane repolarization → clinical basis for use-dependent block by antiepileptics and local anesthetics
Nav Subtypes — Tissue Location and Associated Disorders
| Subtype | Gene | Primary Location | Associated Disorder(s) |
|---|---|---|---|
| Nav1.1 | SCN1A | CNS (inhibitory interneurons) | Dravet syndrome (loss-of-function); GEFS+ |
| Nav1.2 | SCN2A | CNS (axon initial segment, unmyelinated axons) | Early infantile epileptic encephalopathy; benign familial neonatal-infantile seizures |
| Nav1.3 | SCN3A | CNS (embryonic/neonatal brain) | Focal epilepsy (rare) |
| Nav1.4 | SCN4A | Skeletal muscle | Hyperkalemic periodic paralysis; paramyotonia congenita; sodium channel myotonia |
| Nav1.5 | SCN5A | Cardiac muscle | Long QT syndrome type 3; Brugada syndrome |
| Nav1.6 | SCN8A | CNS (nodes of Ranvier) | Epileptic encephalopathy (SCN8A); critical for saltatory conduction |
| Nav1.7 | SCN9A | Peripheral sensory neurons (DRG) | Erythromelalgia (gain-of-function); congenital insensitivity to pain (loss-of-function) |
| Nav1.8 | SCN10A | Peripheral sensory neurons (DRG, nociceptors) | Painful neuropathy; TTX-resistant |
| Nav1.9 | SCN11A | Peripheral sensory neurons (DRG) | Familial episodic pain syndromes; TTX-resistant |
Sodium Channel Blockers
| Agent | Mechanism | Clinical Use |
|---|---|---|
| Tetrodotoxin (TTX) | Blocks Nav pore from extracellular side; blocks Nav1.1–1.7 (Nav1.8, 1.9 are TTX-resistant) | Pufferfish poisoning → ascending paralysis, respiratory failure |
| Saxitoxin | Same mechanism as TTX (pore blocker) | Shellfish poisoning (red tide) → paralysis |
| Local anesthetics (lidocaine, bupivacaine) | Bind intracellular side of Nav; use-dependent block (preferentially block inactivated channels) | Regional anesthesia; block pain fiber conduction |
| Carbamazepine | Stabilizes inactivated state of Nav | Focal epilepsy, trigeminal neuralgia, bipolar disorder |
| Phenytoin | Stabilizes inactivated state of Nav | Focal and tonic-clonic epilepsy |
| Lamotrigine | Stabilizes inactivated state of Nav; also inhibits glutamate release | Broad-spectrum AED; bipolar maintenance |
| Lacosamide | Enhances slow inactivation of Nav (unique mechanism) | Focal epilepsy |
Board Pearl
Dravet syndrome (SCN1A loss-of-function) produces epilepsy because Nav1.1 is preferentially expressed in inhibitory interneurons. Loss of Nav1.1 → impaired interneuron firing → disinhibition → seizures. Na+ channel-blocking AEDs (carbamazepine, phenytoin) can worsen Dravet syndrome by further impairing interneuron function.
Clinical Pearl
Local anesthetics and AEDs (carbamazepine, phenytoin, lamotrigine) share use-dependent block — they preferentially bind the inactivated state of Nav channels. Neurons firing at high frequency (as in seizures or pain) spend more time inactivated, making them more susceptible to blockade. This is why these drugs suppress pathological high-frequency firing while sparing normal activity.
Voltage-Gated Potassium Channels (Kv)
Role in Repolarization
- Delayed rectifier K+ channels (Kv) — open with a delay after depolarization → K+ efflux → repolarization and afterhyperpolarization
- A-type K+ channels — rapidly inactivating; regulate firing frequency and interspike interval
- Ca2+-activated K+ channels (BK, SK) — activated by intracellular Ca2+; contribute to afterhyperpolarization
- KCNQ channels (Kv7, M-current) — slow K+ current that stabilizes resting potential; mutations → epilepsy
Key Kv Subtypes and Clinical Associations
| Channel/Gene | Function | Associated Disorder |
|---|---|---|
| Kv1.1 (KCNA1) | Juxtaparanodal K+ channels; regulate axonal excitability | Episodic ataxia type 1 (EA1) — brief attacks of ataxia + myokymia |
| Kv7.2 (KCNQ2) | M-current; stabilizes resting potential in neurons | Benign familial neonatal seizures (BFNS) |
| Kv7.3 (KCNQ3) | M-current; co-assembles with Kv7.2 | BFNS |
| Kv11.1 (hERG/KCNH2) | Cardiac repolarization | Long QT syndrome type 2 |
| Kir6.2 (KCNJ11) | ATP-sensitive K+ channels in beta cells | Neonatal diabetes; hyperinsulinism |
Potassium Channel Blockers
- 4-Aminopyridine (dalfampridine/fampridine) — blocks Kv channels → prolongs action potential → enhances conduction in demyelinated axons; approved for walking improvement in MS
- Tetraethylammonium (TEA) — non-selective Kv blocker; experimental use
- 3,4-Diaminopyridine (amifampridine) — blocks presynaptic Kv → prolonged depolarization → increased Ca2+ entry → enhanced ACh release; used in Lambert-Eaton myasthenic syndrome
Board Pearl
Episodic ataxia type 1 (EA1) = KCNA1 (Kv1.1) mutation. Presents with brief attacks of ataxia (seconds to minutes) with interictal myokymia (visible muscle rippling). Contrast with EA2 = CACNA1A (P/Q Ca2+ channel) which has longer attacks (hours to days) with interictal nystagmus and responds to acetazolamide.
Voltage-Gated Calcium Channels (Cav)
Subtype Comparison Table
| Type | Gene | Location | Function | Blocker | Associated Disorder |
|---|---|---|---|---|---|
| L-type (Cav1.x) | CACNA1S (Cav1.1), CACNA1C (Cav1.2) | Skeletal muscle, cardiac muscle, smooth muscle, neurons (dendrites/soma) | Excitation-contraction coupling; gene expression | Dihydropyridines (nifedipine, amlodipine); verapamil; diltiazem | Hypokalemic periodic paralysis type 1 (CACNA1S); Timothy syndrome (CACNA1C) |
| N-type (Cav2.2) | CACNA1B | Presynaptic nerve terminals (CNS, PNS) | Neurotransmitter release | ω-Conotoxin | — |
| P/Q-type (Cav2.1) | CACNA1A | Presynaptic terminals (NMJ, cerebellum, CNS) | Neurotransmitter release (dominant at NMJ and cerebellar synapses) | ω-Agatoxin | Lambert-Eaton (P/Q-type Ab); EA2; FHM type 1; SCA6 |
| R-type (Cav2.3) | CACNA1E | CNS neurons (soma, dendrites) | Modulates neurotransmitter release; neuronal excitability | SNX-482 | Epileptic encephalopathy (rare) |
| T-type (Cav3.x) | CACNA1G, 1H, 1I | Thalamic relay neurons, cardiac SA node, neurons | Low-threshold spikes; thalamocortical oscillations; pacemaker activity | Ethosuximide | Absence epilepsy (thalamic T-type → 3 Hz spike-wave); childhood absence epilepsy (CACNA1H) |
Presynaptic Calcium and Neurotransmitter Release
- Action potential arrives at presynaptic terminal → depolarization opens N-type and P/Q-type Ca2+ channels
- Ca2+ influx → binds synaptotagmin (Ca2+ sensor) → triggers SNARE complex-mediated vesicle fusion → neurotransmitter release
- Lambert-Eaton: antibodies against P/Q-type Ca2+ channels at presynaptic terminal → decreased Ca2+ entry → decreased ACh release → proximal weakness, autonomic dysfunction
- Facilitation at high-rate stimulation: residual presynaptic Ca2+ accumulates → progressive increase in NT release → incremental response on repetitive nerve stimulation (unlike MG which decrements)
Board Pearl
CACNA1A (P/Q-type Ca2+ channel gene) is a neurological chameleon — different mutation types cause different diseases: point mutations → FHM type 1 or EA2; trinucleotide (CAG) repeat expansion → SCA6; antibodies against the channel → Lambert-Eaton myasthenic syndrome.
Clinical Pearl
Absence seizures arise from abnormal thalamocortical oscillations driven by T-type Ca2+ channels in thalamic relay neurons. These channels activate at low (hyperpolarized) voltages, generating rhythmic burst firing that produces the characteristic 3 Hz generalized spike-and-wave pattern. Ethosuximide selectively blocks T-type channels, making it first-line for childhood absence epilepsy but ineffective for other seizure types.
Ligand-Gated Ion Channels
Comparison Table
| Receptor | Ion Conducted | Effect | Agonist | Antagonist | Clinical Relevance |
|---|---|---|---|---|---|
| Nicotinic AChR (nAChR) | Na+, K+ | Excitatory (EPSP, muscle contraction) | ACh, nicotine, succinylcholine | Curare, vecuronium, α-bungarotoxin | Myasthenia gravis (Ab to AChR); NMJ blockade; congenital myasthenic syndromes |
| NMDA | Ca2+, Na+ | Excitatory (slow EPSP, LTP) | Glutamate + glycine (co-agonist) | Ketamine, PCP, memantine, Mg2+ (voltage-dependent) | Anti-NMDAR encephalitis; excitotoxicity; LTP/memory |
| AMPA | Na+, K+ | Excitatory (fast EPSP) | Glutamate | Perampanel | Mediates majority of fast excitatory transmission; epilepsy target |
| GABA-A | Cl− | Inhibitory (fast IPSP) | GABA, muscimol | Bicuculline, picrotoxin, flumazenil (BZD-specific) | Epilepsy (target of BZDs, barbiturates); anti-GAD Ab → stiff-person syndrome |
| Glycine | Cl− | Inhibitory (spinal/brainstem) | Glycine | Strychnine | Hyperekplexia (GLRA1 mutations); tetanus (blocks glycine release) |
| 5-HT3 | Na+, K+ | Excitatory | Serotonin | Ondansetron, granisetron | Anti-emetic (chemotherapy); only ionotropic serotonin receptor |
Key Structural Features
- Cys-loop family (pentameric): nAChR, GABA-A, glycine, 5-HT3 — all share a conserved cysteine loop
- Glutamate receptor family (tetrameric): NMDA, AMPA, kainate
- nAChR at NMJ (NM): composed of 2α1, β1, δ, ε subunits; MG autoantibodies typically target the α1 subunit
- GABA-A: most common configuration 2α, 2β, 1γ; BZDs bind at the α/γ interface; GABA binds at the α/β interface
Channelopathies
Master Comparison Table
| Disorder | Gene | Channel | Key Clinical Features |
|---|---|---|---|
| Periodic Paralysis | |||
| Hyperkalemic PP (HyperKPP) | SCN4A | Nav1.4 (skeletal muscle Na+) | Brief attacks (<2 hrs); triggered by rest after exercise, fasting, K+ intake; myotonia between attacks; serum K+ elevated during attack |
| Hypokalemic PP type 1 | CACNA1S | Cav1.1 (skeletal muscle L-type Ca2+) | Prolonged attacks (hours–days); triggered by carbohydrate load, rest after exercise, insulin; serum K+ low during attack |
| Hypokalemic PP type 2 | SCN4A | Nav1.4 | Similar to type 1; less common; SCN4A mutation with different functional effect than HyperKPP |
| Episodic Ataxias | |||
| Episodic ataxia type 1 (EA1) | KCNA1 | Kv1.1 (voltage-gated K+) | Brief attacks (seconds–minutes); interictal myokymia; responds to carbamazepine |
| Episodic ataxia type 2 (EA2) | CACNA1A | Cav2.1 (P/Q-type Ca2+) | Longer attacks (hours–days); interictal nystagmus, progressive ataxia; responds to acetazolamide |
| Myotonias | |||
| Paramyotonia congenita | SCN4A | Nav1.4 | Myotonia worsened by cold and exercise (paradoxical myotonia); face and hands; may have episodic weakness |
| Myotonia congenita (Thomsen/Becker) | CLCN1 | ClC-1 (skeletal muscle Cl− channel) | Muscle stiffness relieved by activity (warm-up phenomenon); Thomsen = AD, Becker = AR (more severe) |
| Epilepsies | |||
| GEFS+ (genetic epilepsy with febrile seizures plus) | SCN1A, SCN1B, GABRG2 | Nav1.1, Nav β1, GABA-A γ2 | Febrile seizures persisting beyond age 6; variable severity within families |
| Dravet syndrome | SCN1A | Nav1.1 (loss-of-function) | Severe infantile epileptic encephalopathy; prolonged febrile seizures; developmental regression; refractory to Na+ channel blockers |
| Benign familial neonatal seizures (BFNS) | KCNQ2, KCNQ3 | Kv7.2, Kv7.3 (M-current) | Seizures in first week of life; self-limited; good prognosis |
| Childhood absence epilepsy | CACNA1A, CACNA1H, GABRG2 | P/Q-type Ca2+, T-type Ca2+, GABA-A | Typical 3 Hz spike-wave; staring spells; ethosuximide first-line |
Board Pearl
Sodium channel-blocking AEDs (carbamazepine, phenytoin, lamotrigine) can worsen Dravet syndrome and myoclonic epilepsies. In Dravet (SCN1A loss-of-function), the remaining Nav1.1 channels on inhibitory interneurons are further blocked, worsening disinhibition and seizures.
Drugs Targeting Ion Channels
Summary Table
| Drug | Channel Target | Mechanism | Clinical Use |
|---|---|---|---|
| Carbamazepine | Nav (fast inactivation) | Stabilizes inactivated state; use-dependent block | Focal epilepsy, trigeminal neuralgia |
| Phenytoin | Nav (fast inactivation) | Stabilizes inactivated state; use-dependent block | Focal and tonic-clonic epilepsy |
| Lamotrigine | Nav; also glutamate release | Stabilizes inactivated state; reduces glutamate | Broad-spectrum AED; bipolar maintenance |
| Lacosamide | Nav (slow inactivation) | Enhances slow inactivation (unique mechanism) | Focal epilepsy |
| Ethosuximide | T-type Ca2+ (Cav3.x) | Blocks low-threshold T-type Ca2+ currents in thalamus | Absence epilepsy (first-line) |
| Gabapentin/Pregabalin | α2δ subunit of Cav | Reduces Ca2+ influx at presynaptic terminals → decreased NT release | Neuropathic pain, epilepsy (adjunctive) |
| Benzodiazepines | GABA-A (Cl−) | ↑ Frequency of Cl− channel opening (requires GABA) | Seizures (acute), anxiety, spasticity |
| Barbiturates | GABA-A (Cl−) | ↑ Duration of Cl− channel opening (can act without GABA) | Refractory status epilepticus |
| Perampanel | AMPA receptor | Non-competitive AMPA antagonist | Focal and generalized tonic-clonic epilepsy |
| Memantine | NMDA receptor | Open-channel blocker (low affinity, uncompetitive) | Moderate-severe Alzheimer's |
| Retigabine (ezogabine) | KCNQ2/3 (Kv7) | Opens Kv7 K+ channels → membrane stabilization | Refractory focal epilepsy (withdrawn due to side effects) |
| 4-Aminopyridine (dalfampridine) | Kv channels | Blocks K+ channels → prolongs AP in demyelinated axons | Walking improvement in MS |
| 3,4-Diaminopyridine (amifampridine) | Presynaptic Kv channels | Blocks K+ channels → prolonged depolarization → ↑ Ca2+ entry → ↑ ACh release | Lambert-Eaton myasthenic syndrome |
| Verapamil/Diltiazem | L-type Ca2+ (Cav1.2) | Blocks cardiac and smooth muscle L-type Ca2+ channels | Hypertension, arrhythmia, migraine prophylaxis |
| Nimodipine | L-type Ca2+ (cerebral vascular) | Selective cerebral vascular dihydropyridine | Vasospasm after subarachnoid hemorrhage |
| Tetrodotoxin (TTX) | Nav (pore blocker) | Blocks Nav from extracellular side | Pufferfish poisoning (no clinical use) |
| Lidocaine | Nav (intracellular) | Use-dependent block; binds inactivated state | Local anesthesia; cardiac arrhythmia |
| Riluzole | Nav; also reduces glutamate release | Inhibits presynaptic glutamate release; blocks Na+ channels | ALS |
Board Pearl
Gabapentin and pregabalin do NOT directly act on GABA receptors. Despite their names, they bind the α2δ auxiliary subunit of voltage-gated Ca2+ channels, reducing presynaptic Ca2+ influx and neurotransmitter release. They are used for neuropathic pain, not as GABAergic drugs.
Clinical Pearl
In Lambert-Eaton myasthenic syndrome, the treatment strategy follows the pathophysiology: antibodies reduce presynaptic P/Q-type Ca2+ channel density → decreased Ca2+ entry → decreased ACh release. 3,4-Diaminopyridine blocks presynaptic K+ channels, prolonging depolarization and allowing more Ca2+ influx through remaining channels → increased ACh release. This is why incremental response is seen on high-rate repetitive stimulation — residual Ca2+ accumulates with rapid firing.
Quick Reference
High-Yield One-Liners
- Resting membrane potential — ~−70 mV; set by K+ leak channels; closest to EK
- Na+/K+ ATPase — 3 Na+ out, 2 K+ in; electrogenic; consumes most neuronal ATP
- Nernst equation — equilibrium potential for one ion; Goldman equation — resting potential for multiple ions
- Nav inactivation gate — basis of absolute refractory period and use-dependent drug block
- SCN1A loss-of-function → Dravet syndrome; avoid Na+ channel blockers
- SCN4A → hyperkalemic PP, paramyotonia congenita, hypokalemic PP type 2
- CACNA1A → EA2, FHM1, SCA6; antibodies to the same channel → Lambert-Eaton
- CACNA1S → hypokalemic periodic paralysis type 1
- KCNA1 → EA1 (brief attacks + myokymia)
- KCNQ2/3 → benign familial neonatal seizures
- CLCN1 → myotonia congenita (Thomsen/Becker); warm-up phenomenon
- T-type Ca2+ channels → thalamic oscillations → absence seizures; ethosuximide
- P/Q-type Ca2+ channels → presynaptic NT release at NMJ; Lambert-Eaton antibody target
- BZDs — ↑ frequency of Cl− opening; Barbiturates — ↑ duration
- 4-AP (dalfampridine) — K+ channel blocker for MS walking; 3,4-DAP — for Lambert-Eaton
- TTX/saxitoxin — pore blockers (extracellular); local anesthetics — intracellular Nav block
Channel Gene Quick-Match Table
| Gene | Channel | Disorder |
|---|---|---|
| SCN1A | Nav1.1 | Dravet, GEFS+ |
| SCN2A | Nav1.2 | Early infantile epilepsy |
| SCN4A | Nav1.4 | HyperKPP, paramyotonia, HypoKPP type 2 |
| SCN5A | Nav1.5 | Long QT type 3, Brugada |
| SCN8A | Nav1.6 | SCN8A epileptic encephalopathy |
| SCN9A | Nav1.7 | Erythromelalgia, congenital pain insensitivity |
| KCNA1 | Kv1.1 | EA1 |
| KCNQ2 | Kv7.2 | BFNS |
| CACNA1A | Cav2.1 (P/Q) | EA2, FHM1, SCA6 |
| CACNA1S | Cav1.1 (L) | HypoKPP type 1 |
| CLCN1 | ClC-1 | Myotonia congenita |
References
- Bhatt A. Ultimate Review for the Neurology Boards. 3rd ed. Demos Medical; 2016. Chapter 1: Neuroscience.
- Blumenfeld H. Neuroanatomy Through Clinical Cases. 3rd ed. Sinauer Associates; 2021.
- Hille B. Ion Channels of Excitable Membranes. 3rd ed. Sinauer Associates; 2001.
- Purves D, et al. Neuroscience. 6th ed. Oxford University Press; 2018.
- Ropper AH, Samuels MA, Klein JP, Prasad S. Adams and Victor's Principles of Neurology. 12th ed. McGraw-Hill; 2023.
- Kullmann DM. Neurological channelopathies. Annu Rev Neurosci. 2010;33:151-172.