6.5-6.7 Membrane Potentials

6.5 Basic Principles of Electricity in Physiology

• Physiological processes follow chemistry and physics laws.

  • Net flux of charged molecules is key.

• Extracellular fluid: predominantly high in sodium (Na^+) and chloride (Cl^-) ions.

• Intracellular fluid: High in potassium (K^+) ions and nonpenetrating ionized molecules (e.g., phosphate compounds, negatively charged proteins).

• Electrical phenomena at plasma membrane are vital for signal integration and cell communication in neurons.

• Like charges repel; opposite charges attract.

Electrical Potential and Current

• Separated opposite charges have electrical potential.

  • Electrical potential: Potential to do work if charges come together; also known as potential difference.

• Unit: Volts (V).

• Biological systems: Use millivolts (mV), where 1 \, mV = 0.001 \, V .

• Current: Movement of electrical charge, driven by electrical potential.

  • opposite charges → current brings both charges together

  • alike charges → current separates them

• Current magnitude:

  • amount of charge that moves

• depends on the potential difference and the material through which charges move.

• Resistance: Hindrance to charge movement; high resistance = low current.

• Ohm’s Law: I = \frac{V}{R} (Voltage (V), current (I), and resistance (R)).

  • High electrical resistance (insulators) reduce current flow. Lipids act as insulators in cell membranes.

  • Low resistance (conductors) allow rapid current flow. Intracellular and extracellular fluids with ions are conductors.

  • Lipid layers of plasma membrane provide high electrical resistance.

6.6 The Resting Membrane Potential

• Neurons at rest: Have a potential difference across plasma membrane (V_m).

  • known as the resting membrane potential

• Inside of cell: Negatively charged relative to outside.

• Extracellular fluid: Voltage reference point; membrane potential polarity is relative to it.

• Example: -70 mV means inside is 70 mV more negative than outside.

• V_m magnitude: Typically -40 to -90 mV in neurons.

Nature and Magnitude of Resting Membrane Potential

• Resting membrane potential exists due to excesses of negative ions inside the cell and positive ions outside.

• Excess charges accumulate in thin shell along plasma membrane surfaces.

• Number of charges needed to establish potential is a tiny fraction of total charges.

Ion Distribution

• Sodium (Na^+) and chloride (Cl^-) concentrations lower inside than outside; potassium (K^+) higher inside.

• Sodium/potassium-ATPase pump (Na^+/K^+-ATPase ): Maintains gradients by pumping Na^+ out and K^+ in.

• Chloride distribution varies among cell types.

• Electrical driving force measured using milliequivalents/L (mEq/L).

Factors Affecting Magnitude of Resting Membrane Potential

• Differences in ion concentrations in intracellular and extracellular fluids.

• Differences in membrane permeabilities to ions via open channels.

• Direct role of ion pumps plays a minor role.

Contribution of Ion Concentration Differences

• Membrane permeable only to K^+ (with K^+ channels open).

• Initially, compartments have equal ion concentrations, no potential difference.

• K^+ diffuses down gradient (high to low), creating potential difference.

• Compartment 1 becomes positively charged, compartment 2 negatively charged.

• Membrane potential influences K^+ movement; negative charge attracts K^+.

• Electrochemical gradient exists for all ions.

• Equilibrium potential for K^+ when fluxes balance; no net movement.

• Membrane potential generated with concentration gradient and open K^+ channels.

• Equilibrium established by insignificant ion number.

• Equilibrium potential magnitude depends on ion concentration gradient.

Nernst Equation

• Calculates equilibrium potential using ion concentration gradient.

• E{ion} = 61 \times log\left(\frac{C{out}}{C_{in}}\right)

  • E_{ion} = equilibrium potential for a particular ion (mV)

  • C_{in} = intracellular concentration of the ion

  • C_{out} = extracellular concentration of the ion

  • z = valence of the ion

  • 61 = a constant value incorporating the universal gas constant, temperature (37°C), and Faraday electrical constant

• Typical concentrations: Na^+ flux brings membrane potential to +60 mV, K^+ flux to -90 mV.

Contribution of Different Ion Permeabilities

• Membrane potential depends on permeabilities and concentration gradients of all ions when multiple channels are open.

• Greater the membrane permeability to an ion, the greater its contribution to the membrane potential.

• Goldman-Hodgkin-Katz (GHK) equation calculates resting membrane potential (Vm): Vm = 61 \times log\left(\frac{PK[K^+]{out} + P{Na}[Na^+]{out} + P{Cl}[Cl^-]{in}}{PK[K^+]{in} + P{Na}[Na^+]{in} + P{Cl}[Cl^-]{out}}\right)

• GHK equation accounts for individual ion permeabilities.

• Ion gradients and permeabilities vary in different excitable cells.

• Mammalian neurons: K^+ permeability is much greater than that for Na^+ and Cl^- , so the resting membrane potential is close to the equilibrium potential for K^+.

• Chloride (Cl^-) has minimal importance compared to K^+ and Na^+.

Resting Potential Generation

• Largely by K^+ movement out of cell via leak channels, making inside negative.

• Resting membrane potential not equal to K^+ equilibrium potential because some open leak channels for Na^+ pull the membrane potential towards the Na^+ equilibrium potential.

• The Na^+/K^+-ATPase pump maintains stable concentrations of intracellular sodium and potassium ions by balancing the leak of ions down their electrochemical gradients.

Contribution of Ion Pumps

• Na^+/K^+-ATPase pump maintains concentration gradients.

• Pump directly contributes to negative resting potential by moving three Na^+ out for every two K^+ in (electrogenic pump).

• Electrogenic contribution is small but vital.

Development of Resting Membrane Potential

• Na^+/K^+-ATPase pump establishes concentration gradients, determining equilibrium potentials, and has small electrogenic effect.

• Greater K^+ efflux than Na^+ influx results in negative membrane potential due to higher permeability to K^+.

• Steady-state: Dynamic balance is reached with equal inward and outward currents maintaining a steady membrane potential.

• The Na^+/K^+-ATPase pump balances ion movement to maintain concentration gradients.

• In cells without chloride pumps, Cl^- concentrations shift until the equilibrium potential for Cl^- equals the resting membrane potential.

• Some cells have nonelectrogenic active-transport systems that move Cl^- out of the cell, creating a Cl^- equilibrium potential negative to the resting membrane potential, contributing to the excess negative charge inside the cell.

Key Concepts

• Resting membrane potential: Electrical potential difference across plasma membrane, generated by ion concentration differences and membrane permeabilities.

• Equilibrium potential: Membrane potential at which concentration and electrical forces on an ion are equal.

• GHK equation: Calculates membrane potential with known ion concentrations and permeabilities.

• Na+/K+-ATPase pumps: Maintain low intracellular Na^+ and high intracellular K^+ concentration via active transport; contribute directly as an electrogenic pump.

Graded Potentials and Action Potentials

• Cells generate electrical signals via gated ion channels, changing membrane potential.

• Excitability: Ability of a cell to produce electrical signals.

• Graded potentials: Important for short-distance signaling.

• Action potentials: Long-distance signals in neuronal and muscle cell membranes.

Terms Describing Changes in Membrane Potential

• Depolarize: Membrane potential becomes less negative.

• Overshoot: Reversal of membrane potential polarity.

• Repolarize: Membrane potential returns to resting value.

• Hyperpolarize: Membrane potential becomes more negative.

Graded Potentials

• Changes in membrane potential confined to small region.

• Magnitude varies.

• Examples: receptor, synaptic, and pacemaker potentials.

• Local current flow spreads depolarization.

• Charge is lost across the membrane, and potential decreases with distance.

• Local current flow is decremental, decreasing with distance.

• Summation: Additional stimuli add to potential.

Action Potentials

• Significant changes in membrane potential.

• Rapid and repeat at high frequencies.

• Mechanism: Propagation down the axon is communication in the nervous system.

Voltage-Gated Ion Channels

• Regulate ion channel opening.

• Mediate graded potentials as initial stimulus for action potential.

• Types: Conduct Na^+, K^+, Ca^{2+}, Cl^-; behavior varies with voltage.

• Depolarization opens channels; negative potential keeps them closed.

• Sodium channels open faster than potassium channels.

  • Voltage-gated Na+ channels contain an inactivation gate, which limits Na+ flux by blocking the channel shortly after depolarization opens it.

Action Potential Mechanism

• Transient changes in membrane permeability allow ions to move down gradients.

• Depolarizing stimulus: Neurotransmitter binds to ligand-gated ion channel, allowing Na^+ entry.

  • Positive Feedback Loop: Na^+ entry causes depolarization, opening more voltage-gated Na^+ channels.

  • Absolute Refractory Period: Na^+ permeability declines as inactivation gates block open Na^+ channels.

  • Voltage gated K^+ channels open: Increases K^+ flux out of the cell - repolarizes the membrane toward its resting value

  • Afterhyperpolarization – K^+ permeability remains above resting levels and the membrane is transiently hyperpolarized toward the K^+ equilibrium potential

  • Voltage-gated Na+ channels operate in a positive feedback mode at the action potential's beginning, while voltage-gated K+ channels trigger the action potential's conclusion via a negative feedback process.

Threshold Potential

• Action potentials occur only when stimulus elevates membrane potential beyond threshold.

• Threshold stimuli are strong enough to depolarize the membrane to the threshold potential.

• Subthreshold potentials: Weak depolarizations, no action potential.

• Stronger stimuli elicit the same amplitude action potentials.

All-or-None Principle

• Action potentials occur maximally or not at all.

• Frequency and patterns of action potentials provide stimulus magnitude information.

• Local anesthetics (e.g., procaine, lidocaine) block voltage-gated Na^+ channels, preventing transmission of graded signals.

Refractory Periods

• Absolute Refractory Period: Further stimulation won't cause another action potential because Na^+ channels are open or inactivated.

• Relative Refractory Period: A second action potential can be elicited only if the stimulus strength is greater than normal due to some Na^+ channels being in a resting state and K^+ channels still being open.

• Refractory periods limit the number of action potentials an excitable membrane can produce in a given time.

Action Potential Propagation

• Action potential travels the neuron if each point is depolarized to threshold.

• Potential differences cause current flow, depolarizing adjacent membrane and opening voltage-gated Na^+ channels.

• Each regeneration depends on the positive feedback cycle of a new group of Na^+ channels.

• Action potentials are not decremental

• Action potential propagation is away from a region of membrane recently active.

• Excitatory membranes can conduct action potentials in either direction if the membrane through which the action potential must travel is not refractory

Myelination

• Action Potential Velocity: Depends upon fiber diameter and myelination.

• Membrane pumps need to restore fewer ions; less charge leaks, and more arrives at the adjacent node.

• Myelinated axons are metabolically more efficient.

• Action potentials appear to jump from node to node - saltatory conduction.

• Conduction velocities range from 0.5 m/sec for small-diameter, unmyelinated fibers to 100 m/sec for large-diameter, myelinated fibers.

Generation of Action Potentials

• Threshold potential must be attained.

• In afferent neurons, receptor potentials generate initial depolarization

• Action Potential Initiators:

  • Synaptic input to the neuron, known as a synaptic potential.

  • Spontaneous change in the neuron’s membrane potential, known as a pacemaker potential.

Key concepts

*Neurons are excitable

*Graded potentials - local potentials with magnitudes that can vary are decremental

*Action potential - large change in membrane potential- membrane depolarizes and then repolarizes

*Myelination results in Saltatory conduction – regeneration of action potentials only at nodes of Ranvier