# Ion Channels

> Ion channels in MBBS Biochemistry: gating classes, selectivity filter, patch clamp, Nernst potentials, channelopathies and targets from lidocaine to nifedipine.

- Canonical URL: https://prepelephant.com/topics/mbbs/biochemistry/ion-channels-biochemistry
- Exam / course: MBBS · Subject: Biochemistry
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-02
- Last updated: 2026-10-02
- How to cite: "Ion Channels", PrepElephant, https://prepelephant.com/topics/mbbs/biochemistry/ion-channels-biochemistry

## Direct answer

A potassium channel can pass up to a hundred million ions per second while refusing the smaller sodium ion — selectivity without tight binding, achieved by a selectivity filter of backbone carbonyls that mimics potassium's hydration shell so well that sodium, too small and wrongly spaced, cannot pay its dehydration cost. Channels are classified by gating: voltage-gated (the sodium, calcium and potassium channels of excitable membranes, sensing voltage with a positively charged S4 helix), ligand-gated (nicotinic receptor, GABA-A, NMDA — ionotropic, and not to be conflated with G-protein-coupled metabotropic receptors), and mechanosensitive channels. Patch clamp, devised by Neher and Sakmann, records single-channel currents and proved transitions between discrete open and shut states. Mutations of channel genes — channelopathies — underlie long QT syndromes, periodic paralyses and myotonias.

## What you must remember

- **Gating triad:** voltage-gated (S4 positive charges as the sensor), ligand-gated (ionotropic receptors), mechanosensitive — with ionotropic-versus-metabotropic as the distinction examiners insist upon.
- **Selectivity chemistry:** the potassium filter's TVGYG carbonyl ring dehydrates and lines up K+ but not the smaller Na+; channels conduct 10^6-10^8 ions per second versus about 10^2-10^4 for pumps and carriers.
- **Sodium channel anatomy:** one large alpha subunit of four homologous domains, each with six transmembrane helices; the DIII-DIV linker is the inactivation ball that plugs the pore; tetrodotoxin blocks from outside, local anaesthetics from inside — use-dependently.
- **Use-dependent block:** lidocaine binds open and inactivated channels preferentially, so rapidly firing fibres are blocked first — the basis of both anaesthesia and class Ib antiarrhythmic action.
- **Calcium channel subtypes:** L-type in cardiac and smooth muscle (dihydropyridines such as nifedipine act vascularly; verapamil and diltiazem act on the heart), N- and P/Q-type at transmitter release sites.
- **Potassium channel variety:** voltage-gated Kv, inward rectifiers, and the KATP channel — Kir6.2 plus SUR1, the sulphonylurea receptor that gliclazide-type drugs block to release insulin.
- **Channelopathy map:** LQT1 (KCNQ1, IKs loss, swimming), LQT2 (KCNH2/hERG, auditory startle), LQT3 (SCN5A gain of function, events at rest), hyperkalaemic periodic paralysis (SCN4A), myotonia congenita (CLCN1 chloride), malignant hyperthermia (RYR1).
- **Equilibrium arithmetic:** Nernst potential at 37 degrees Celsius is 61.5 divided by valency times the log of outside-over-inside concentration — for potassium, about -90 mV; multiple ions demand the Goldman equation.

## Three long QT types, one dose of logic

Each long QT syndrome removes or adds a current, and the genotype explains the trigger. LQT1 loses the slow potassium current IKs (KCNQ1) — the current that repolarises the heart during adrenergic stress — so syncopal events strike during swimming and exercise, and beta-blockers are the core therapy. LQT2 loses hERG current (KCNH2), vulnerable to auditory startles and emotional arousal; its drug-induced impersonator matters as much — a long blacklist of medicines from certain antiemetics to some antipsychotics block hERG, which is why every new drug faces hERG screening. LQT3 is the gain-of-function inversion: persistent late sodium current (SCN5A) delays repolarisation worst at slow rates, events arriving during sleep, and mexiletine — a sodium-channel blocker that trims the late current — specifically helps. Treatment follows biophysics: beta-blockade for adrenergic types, late-sodium blockade for LQT3, defibrillator for the high-risk. One membrane current per gene per lifestyle trigger — channelopathies are where physiology becomes personalised medicine.

## Where students slip

Ionotropic versus metabotropic is the perennial one-mark loss: the nicotinic receptor is a channel carrying current itself; the muscarinic receptor is a G-protein-coupled receptor acting through second messengers — name both receptors at the synapse to prove the point. Second, "channels use ATP" — false; channels are passive, downhill, electrochemical-gradient devices (KATP is named for its regulator, not its fuel). Third, the Nernst equation is quoted without valency or temperature adjustments; write the 61.5/z form and substitute potassium concentrations to show the -90 mV resting contribution. Finally, anaesthesia questions reward the fibre-order fact — small myelinated fibres (pain) before large ones, explaining perioral numbness and tinnitus as early lidocaine toxicity — a pharmacology-biochemistry bridge frequently asked in Indian postgraduate examinations.

## Frequently asked questions

### Why does a potassium channel admit K+ but not the smaller Na+?

The selectivity filter's carbonyl oxygens are spaced to substitute for potassium's water shell; sodium is too small to contact them and cannot pay the energy cost of partial dehydration.

### What is use-dependent blockade by local anaesthetics?

Preferential binding to open and inactivated sodium channels, so rapidly firing nerve and cardiac fibres are blocked first — explaining selective analgesia and class Ib antiarrhythmic action.

### Which currents are lost in LQT1 and LQT2?

LQT1 loses the slow delayed rectifier IKs (KCNQ1), LQT2 the rapid rectifier through hERG (KCNH2) — both delaying repolarisation, one triggered by exertion, the other by auditory startle.

### What is the KATP channel, and why does it matter in diabetes?

An ATP-sensitive potassium channel (Kir6.2 plus SUR1) closing when ATP rises; sulphonylureas close it via SUR1, depolarising the beta cell and releasing insulin.

### What did patch clamp recording demonstrate?

Erwin Neher and Bert Sakmann's technique (Nobel 1991) recorded current through single channel molecules, proving discrete all-or-none openings with defined conductance states.