Ion Channels
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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.