Resting Membrane Potential Overview

Resting Membrane Potential

• Defined as the voltage difference across the cell membrane when a neuron is at rest.
• Exists in all cell types, not just neurons, highlighting its universal biological significance.
• Typical range for resting membrane potential in neurons is between negative 70 to negative 90 millivolts, with negative 70 millivolts being the average.

Mechanisms Contributing to Resting Membrane Potential

• Sodium-Potassium ATPases

  • Pumps three sodium ions out of the cell and two potassium ions into the cell.
  • Establishes a slight negative charge inside the cell and maintains ion concentration gradients: higher sodium outside and higher potassium inside.

• Leaky Potassium Channels

  • Always open, allowing potassium ions to flow in and out of the cell passively.
  • Higher potassium concentration inside drives potassium ions to exit, leading to a more negative internal environment.
  • Loss of potassium creates unoccupied negative charges (anions) inside, increasing negativity up to around negative 90 millivolts.

• Leaky Sodium Channels

  • Also allow sodium ions to flow, but the permeability of the membrane to potassium is much higher than that to sodium.
  • Sodium influx contributes less to resting membrane potential adjustment, as much of its concentration remains outside the cell.

Ion Concentration Gradients

• Sodium concentration is higher outside, while potassium concentration is higher inside due to the action of pumps.
• The movement of ions occurs based on their respective concentration gradients, contributing to the overall membrane potential.

Nernst Potential

• Calculated for various ions (e.g., potassium and sodium) to determine their equilibrium potential across the membrane.
• For potassium:
  • Equation used: E(K) = 61.5 / z × log([K outside] / [K inside])
  • Typical concentrations: 5 mM outside, 150 mM inside yield approximately negative 90 millivolts.
• For sodium:
  • Equation: E(Na) = 61.5 / z × log([Na outside] / [Na inside])
  • Typical concentrations: 140 mM outside, 10 mM inside yield approximately positive 70 millivolts.

Overall Impact

• The resting membrane potential is determined primarily by the equilibrium potentials of potassium and sodium.
• Significant shifts in membrane potential are primarily due to changes in permeability to potassium, rather than sodium, emphasizing the greater impact of potassium on resting potential stabilization.### Membrane Potentials
• Resting membrane potential is typically around negative 70 millivolts.
• The equilibrium potential for potassium influences the cell voltage when potassium ions move out.
• A cell with 90% permeability to potassium and 10% to sodium would average near negative 70 millivolts.

Graded Potentials

• Graded potentials adjust the resting membrane potential towards the threshold for action potentials.
• Threshold voltage for action potential stimulation is approximately negative 55 millivolts.
• Depolarization moves the membrane potential closer to threshold; hyperpolarization makes it more negative.
• Excitatory postsynaptic potentials (EPSPs) bring the membrane potential closer to threshold.
• Inhibitory postsynaptic potentials (IPSPs) move the potential further from threshold.

Neuronal Communication

• Presynaptic neurons release neurotransmitters (e.g., glutamate for EPSPs, GABA for IPSPs) at the synapse to influence the postsynaptic neuron.
• Ligand-gated ion channels open in response to neurotransmitter binding, allowing ion flow.
• Sodium (Na+) and calcium (Ca2+) influx increases the cell's positive charge.
• Chloride (Cl-) influx or potassium (K+) efflux makes the cell interior more negative, inducing hyperpolarization.

Summation of Potentials

• EPSPs and IPSPs compete to influence membrane potential, with the aim to have more EPSPs to trigger action potentials.
• Temporal summation involves rapid repeated firing from a single presynaptic neuron, cumulatively raising potential.
• Spatial summation involves simultaneous firing from multiple presynaptic neurons, increasing total EPSP effect.

Threshold and Action Potential

• Action potentials are triggered when the threshold of negative 55 millivolts is reached at the axon hillock.
• Voltage-gated sodium channels, concentrated at the axon hillock, open rapidly upon reaching threshold.
• Sodium influx during action potential can elevate membrane potential to positive 30 millivolts, reversing the polarity.
• Once the threshold is reached, voltage-gated channels create an all-or-nothing response, triggering the action potential.### Action Potential and Ion Channels
• Resting Membrane Potential: Neurons have a resting membrane potential around -70 millivolts.
• Threshold Potential: An action potential is initiated when the membrane potential reaches approximately -55 millivolts.
• Voltage-Gated Sodium Channels:
  • Activation gate opens at -55 millivolts, allowing sodium (Na+) ions to rush in.
  • Positive feedback leads to rapid depolarization, peaking around +30 millivolts.
  • Inactivation gate closes at +30 millivolts, preventing further Na+ entry.

Depolarization and Action Potential Propagation

• Depolarization: Movement from a negative to a positive internal charge, specifically when Na+ enters the cell.
• Propagation: The depolarizing wave moves along the axon towards the terminal bulb.
• Voltage-Gated Calcium Channels: Activated at +30 millivolts, allowing calcium (Ca2+) to enter the axon terminal necessary for neurotransmitter release.

Neurotransmitter Release Mechanism

• Synaptic Vesicle Fusion: Calcium binds to SNARE proteins, facilitating the fusion of vesicles with the cell membrane.
• Exocytosis: Release of neurotransmitters into the synaptic space to interact with adjacent neurons.

Repolarization and Hyperpolarization

• Repolarization: Returning the membrane potential back to resting state (-70 millivolts).
• Voltage-Gated Potassium Channels: Open at +30 millivolts, allowing potassium (K+) to exit and move the potential towards -90 millivolts.
• Hyperpolarization: Occurs when the potential goes below -70 millivolts due to excess K+ leaving before returning to resting potential.

Key Definitions

• Depolarization: Making the inside of the cell more positive.
• Repolarization: Returning from a positive back to a negative resting potential.
• Hyperpolarization: Increasing negativity beyond the resting potential.

Recovery to Resting Membrane Potential

• Restoration Mechanisms: Involvement of sodium-potassium ATPase and leak channels help stabilize the membrane potential back to -70 millivolts.
• Refractory Periods:
  • Absolute Refractory Period: Follows peak depolarization where no stimulation can initiate another action potential, regardless of stimulus strength.
  • Relative Refractory Period: Occurs after the absolute phase when a stronger-than-normal stimulus is needed to initiate a new action potential.

Summary of Voltage-Gated Channel States

• At Rest: Activation gate closed, inactivation gate open.
• During Depolarization: Activation gate opens, inactivation gate begins to close.
• At Peak Depolarization: Activation gate open, inactivation gate closed.
• During Repolarization: Activation gate begins to close, K+ channels open.
• Post Action Potential: Recovery to resting state configuration upon reaching -70 millivolts.

Resting Membrane Potential

• Voltage difference across the cell membrane in a resting neuron, typically around -70 to -90 millivolts.
• Universal phenomenon observed in all cell types, not just neurons.

Mechanisms Contributing to Resting Membrane Potential

• Sodium-Potassium ATPases: Pumps 3 Na+ ions out and 2 K+ ions in, creating a slight negative interior and maintaining concentration gradients.
• Leaky Potassium Channels: Always open, allowing K+ to exit, enhancing negative charge inside the cell.
• Leaky Sodium Channels: Less impact on resting potential due to lower permeability; primarily sodium remains outside.

Ion Concentration Gradients

• Sodium concentration is higher outside (140 mM) and potassium is higher inside (150 mM).
• Ion movement driven by these gradients influences membrane voltage.

Nernst Potential

• Equilibrium potential calculated to determine ion movement across membranes.
• Potassium: E(K) calculation shows potential around -90 mV based on typical ion concentrations.
• Sodium: E(Na) is approximately +70 mV based on differing concentrations inside and outside.

Overall Impact

• Resting membrane potential highly influenced by potassium equilibrium potential and its permeability.
• Shifts in membrane potential primarily occur due to changes in potassium permeability rather than sodium.

Membrane Potentials

• Average resting membrane potential is about -70 mV.
• Higher potassium permeability results in a more stable resting potential around this value.

Graded Potentials

• Facilitate adjustments to resting potential, moving towards action potential threshold of approximately -55 mV.
• EPSPs bring the potential closer to threshold while IPSPs push it further away.

Neuronal Communication

• Neurotransmitters (e.g., glutamate for EPSPs, GABA for IPSPs) released by presynaptic neurons impact the postsynaptic neuron.
• Ligand-gated ion channels open upon binding of neurotransmitters, allowing ion flow that alters charge inside the neuron.

Summation of Potentials

• EPSPs and IPSPs balance to affect membrane potential; more EPSPs needed to trigger action potentials.
• Temporal summation combines rapid sequential firing from a single neuron.
• Spatial summation accumulates effects from concurrent firings of multiple neurons.

Threshold and Action Potential

• Action potential triggered at -55 mV at axon hillock, where voltage-gated sodium channels open.
• Rapid depolarization occurs as Na+ influx raises potential to +30 mV, reversing polarity.

Action Potential and Ion Channels

• Resting membrane potential around -70 mV; action potential initiation requires reaching the threshold.
• Voltage-gated sodium channels rapidly open at threshold, allowing Na+ entry and causing depolarization.

Depolarization and Action Potential Propagation

• Depolarization occurs when Na+ floods into cells, creating a positive charge.
• Propagation of depolarization signals travels along the axon toward the terminal.
• Voltage-gated calcium channels open at +30 mV, critical for neurotransmitter release.

Neurotransmitter Release Mechanism

• Calcium binds to SNARE proteins aiding vesicle fusion with the membrane for exocytosis of neurotransmitters.

Repolarization and Hyperpolarization

• Repolarization brings the membrane back to about -70 mV.
• Voltage-gated potassium channels open at +30 mV, causing K+ to exit and potential to drop towards -90 mV.
• Hyperpolarization occurs when the potential falls below -70 mV due to excess K+ outflow.

Key Definitions

• Depolarization: Inside of cell becomes more positive.
• Repolarization: Return from a positive back to negative resting potential.
• Hyperpolarization: Increased negativity beyond resting potential.

Recovery to Resting Membrane Potential

• Sodium-potassium ATPase and leak channels help stabilize the membrane back to -70 mV.
• Refractory Periods:
  • Absolute Refractory Period: No further action potentials can be initiated post-depolarization.
  • Relative Refractory Period: Follows absolute period; requires a stronger stimulus to generate a new action potential.

Summary of Voltage-Gated Channel States

• At Rest: Activation gates closed, inactivation gate open.
• During Depolarization: Activation gate opens; inactivation gate starts closing.
• At Peak: Both activation gates are open; inactivation gate closes to stop Na+ entry.
• During Repolarization: K+ channels open, returning the cell to a negative state.
• Post Action Potential: Channels recover to resting state configuration as the potential returns to -70 mV.