Passive & Active Membrane Transport, Resting and Action Potentials

Passive Membrane Transport

  • Fundamental definition- Passive = no direct expenditure of metabolic energy (ATP).

    • Net movement is always “downhill,” i.e. from regions of high electro-chemical potential to low electro-chemical potential.

    • Three sub-modes

    • Simple diffusion through the lipid bilayer.

    • Facilitated diffusion via carrier proteins.

    • Diffusion through ion channels.

Simple Diffusion

  • Permits small, non-polar, or highly lipid-soluble substances to permeate freely.- O2, CO2, steroid hormones, many lipophilic drugs, and even H2O in limited amounts.

  • Governing parameter is flux (rate of transfer per unit area)- Units: mol·cm-2·s-1.

    • Flux J is proportional to (delta C) x A / d where

    • delta C = concentration gradient (steepness => faster).

    • A = cross-sectional/interface area.

    • d = diffusion distance/thickness (greater => slower).

    • Molecular size/weight inversely affects diffusivity (large => slower).

  • Diffusion proceeds until equilibrium (no net flux, though random motion continues).

Facilitated Diffusion (Carrier-Mediated)

  • Used by polar, uncharged solutes too large or hydrophilic for the bilayer.

  • Requires integral membrane proteins (uniporters) that bind the solute, undergo conformational change, and release it on the opposite side.

  • Saturable (transport maximum), subject to competition and specificity.

  • Example: glucose entry via GLUT1.- Raised plasma [glucose] establishes a chemical driving force for influx.

    • Sequence: binding -> conformational flip -> release inside.

    • Critical for ATP production in almost every cell.

Diffusion Through Ion Channels

  • Channels are transmembrane proteins containing water-filled pores.

  • Permit rapid, selective diffusion of ions (Na+, K+, Cl-, Ca2+) down electrochemical gradients.

  • Selectivity filter determines which ions permeate; gate controls open/closed state.

  • Driving forces- Chemical (concentration) gradient.

    • Electrical gradient (membrane potential Vm):

    • Negative Vm repels anions, attracts cations.

  • Types of channel gating- Leak (non-gated): randomly open; maintain resting potentials (e.g., K+ leak).

    • Ligand-gated: open when specific chemical (e.g., acetylcholine) binds.

    • Mechanically gated: respond to mechanical stress/stretch.

    • Voltage-gated: respond to changes in Vm (critical for action potentials).

  • Example: high extracellular [Na+] (+145 mM) -> Na+ influx through open Na+ channel when present.

Osmosis (Passive Diffusion of Water)

  • Water moves down its water concentration gradient (equivalently up its solute gradient).

  • Cell membrane permeability to water dramatically increased by aquaporins.

  • Tonicity definitions- Isotonic (≈0.9 % NaCl) – no net water flux.

    • Hypotonic – extracellular fluid less concentrated; water influx -> cell swelling.

    • Hypertonic – extracellular fluid more concentrated; water efflux -> cell shrinkage.

  • Frog-egg experiment- Injecting AQP1 into Xenopus oocytes rendered them highly water-permeable; immersion in fresh water caused swelling and lysis.

Key Take-Home Principles of Passive Transport

  1. Requires a pathway (permeability) + a driving force (chemical and/or electrical).

  2. No direct ATP consumption; movement is always toward equilibrium.

Active Membrane Transport

  • Characterised by “uphill” transport against chemical or electrochemical gradients.

  • Necessitates metabolic energy and specialised pump proteins.

  • Two mechanistic classes1. Primary active transport – direct coupling to ATP hydrolysis.

    1. Secondary active transport – indirect; uses energy stored in another solute’s gradient.

Primary Active Transport – Na+ /K+-ATPase ("Na Pump")

  • Stoichiometry: each catalytic cycle exports 3 Na+ and imports 2 K+ (net +1 positive charge out -> electrogenic).

  • Universally expressed; consumes a major fraction of cellular ATP (especially in excitable tissues).

  • Establishes and maintains steep transmembrane gradients:- Extracellular: Na+ ≈ 145 mM, K+ ≈ 4 mM.

    • Intracellular: Na+ ≈ 15 mM, K+ ≈ 140 mM.

  • Essential for volume regulation, secondary transport, and excitability.

Secondary Active Transport

  • Harnesses the potential energy of Na+ gradient (generated by Na pump).

  • Transporter binds Na+ + another solute.- Symport (co-transport): both species move same direction (e.g., Na+-glucose in intestine/kidney).

    • Antiport (counter-transport): solutes move opposite directions (e.g., Na+-Ca2+ exchanger).

  • Net effect: secondary solute is moved against its gradient without direct ATP use.

Vesicular Transport (Bulk Flow)

  • Exocytosis – fusion of secretory vesicle with plasma membrane; releases neurotransmitters, hormones, enzymes. ATP-dependent.

  • Endocytosis – plasma membrane invaginates to internalise material.- Receptor-mediated endocytosis (specific ligands).

    • Phagocytosis (large particles, pseudopodia).

    • Pinocytosis/bulk-phase.

  • Transcytosis – vesicle moves substance across a cell, entering on one side and exiting the other.

Summary of Active Principles

  1. Active transport moves solutes uphill using energy.

  2. Primary = direct ATP hydrolysis; Secondary = exploits existing gradient.

  3. Na pump crucial for ionic gradients, osmotic balance, and excitability.

  4. Vesicular pathways handle macromolecules and bulk substances.

Membrane Potentials (Resting Vm)

  • All living cells display electrical polarisation: inside negative relative to outside.

  • Convention: Vm is measured inside minus outside (outside set to 0).

  • Ingredients required1. Concentration gradients – principally from Na pump activity.

    1. Selective permeability – mainly via leak K+ channels.

Establishing the Resting Potential

  • Na pump creates high intracellular K+ and low intracellular Na+.

  • Opening of K+ leak channels => K+ efflux down its chemical gradient.- Leaves behind impermeant anions -> interior becomes negative.

  • Electrical gradient develops opposing further K+ loss.

  • Equilibrium when chemical and electrical forces balance: described by the Nernst equation.- For K+ (given concentrations above): EK is approximately -95 mV.

    • For Na+: ENa is approximately +60 mV.

  • Real cells permeable to both ions have Vm between these extremes; exact value depends on relative permeabilities (Goldman–Hodgkin–Katz equation concept).

Conceptual Points

  • Only a tiny separation of charge across the membrane (<<1 % of total ions) is needed to establish Vm.

  • Altering permeability (opening/closing channels) rapidly changes Vm – foundational for excitability.

Nerve Action Potentials (APs)

  • Nobel-prize work of Hodgkin & Huxley elucidated ionic basis.

  • AP = rapid (~2 ms), stereotyped swing of Vm (~−70 mV -> +30 mV -> −70 mV).

Phases & Ion Channel Dynamics

  1. Resting state- Voltage-gated Na+ activation gates closed; inactivation gates open.

    • Voltage-gated K+ gates closed.

  2. Depolarisation (upstroke)- Membrane depolarisation opens Na+ activation gates -> massive Na+ influx (drives Vm toward ENa).

  3. Peak / Early Repolarisation- Na+ channels inactivate (inactivation gate closes) halting Na+ influx.

  4. Repolarisation- K+ channels, which open more slowly, now fully open -> K+ efflux returns Vm toward EK.

  5. After-hyperpolarisation / Return to Rest- K+ channels slowly close; Na+ channels reset (inactivation gate reopens, activation gate closes), restoring resting configuration.

Refractoriness

  • Absolute refractory period: Na+ channels inactivated; no new AP possible.

  • Relative refractory period: some K+ channels still open; a larger stimulus is required.

Functional Significance

  • APs are the elementary signals of the nervous system; amplitude-coded, all-or-none events enabling rapid, long-distance communication.

  • Depend entirely on passive & active membrane properties previously discussed (ion gradients, selective permeability, voltage-gated channels).

Integrative Connections & Practical Relevance

  • Disorders of passive transport: cystic fibrosis (defective Cl- channel), water balance disturbances (aquaporin mutations).

  • Na pump inhibition by cardiac glycosides (digoxin) increases intracellular Ca2+ via Na+-Ca2+ exchanger—therapeutic in heart failure.

  • IV fluid selection (isotonic vs hypotonic) must account for osmosis to avoid erythrocyte lysis or shrinkage.

  • Local anaesthetics block voltage-gated Na+ channels, preventing action potentials and pain transmission.

  • Energy cost: nervous tissue’s high ATP use largely funds Na pump activity; hypoxia rapidly compromises Vm and neuronal function.

Compact Checklist of Core Equations & Numbers

  • Flux: J = -D * (partial C / partial x) (Fick) -> qualitative.

  • Na pump stoichiometry: 3 Na+ in + 2 K+ out + ATP -> 3 Na+ out + 2 K+ in + ADP + Pi.

  • Nernst: Eion = (RT / zF) * ln([ion]out / [ion]in).

  • Representative potentials: EK is approximately -95 mV, ENa is approximately +60 mV, Vrest is approximately -70 mV.

  • Osmolar equivalence: 0.9 % NaCl ≈ 290 mOsm·L-1 (isotonic).

Final Synthesis

  • Passive and active transport processes collaborate to shape cellular environments and electrical behaviour.

  • Manipulating permeability (opening channels) converts subtle ionic gradients into dynamic electrical signals (action potentials).

  • Continuous Na pump activity underlies all higher nervous, muscular, and secretory functions, highlighting the inseparability of bioenergetics and information processing in physiology.