Excitabilidad (Parte 1) - Biología Celular y Tisular

Name: Excitabilidad (Parte 1) - Biología Celular y Tisular
Uploaded: 2022-04-08T12:58:51.000Z
Duration: 1 h 40 min 57 s

Introduction to Biophysical Bases of Excitability

Overview of Previous Class

The previous class covered the characteristics of substance transport across membranes, focusing on biological membrane structures and their impermeability to ions and polar solutes.

One key function discussed was compartmentalization, which separates environments with different compositions, such as intracellular and extracellular spaces.

Membrane Potential Concepts

The cell's interior has a net negative charge due to proteins, creating a symmetry of charges that can be measured as a potential difference.

A voltmeter measures this potential difference using a fine-tipped glass electrode that penetrates the cell without causing damage.

Defining Membrane Potential

By convention, the external potential is set at zero; thus, the difference between internal and external potentials defines the resting membrane potential.

Resting membrane potentials vary by cell type, typically ranging from -40 mV to -90 mV. This value remains constant under physiological conditions unless altered by specific stimuli.

Action Potentials in Excitable Cells

Certain cells like neurons and muscle fibers can rapidly change their membrane potential in response to chemical, electrical, or mechanical stimuli.

These changes propagate as action potentials along nerve fibers or muscle tissues when triggered by sufficient stimulus intensity.

Passive vs. Active Phenomena in Cellular Excitability

Circuit Analogy for Cell Function

The lipid bilayer acts as an insulator while surrounding media (intracellular and extracellular fluids) are conductors; this setup allows for charge movement across the membrane.

The membrane can be modeled as a parallel plate capacitor where conductive plates represent intra/extracellular media and the insulating layer is the lipid bilayer.

Role of Ion Channels

Proteins embedded in the bilayer serve as ion channels facilitating ion passage; these channels can be represented as resistances within our circuit model.

Both resistance (ion channels' effects on current flow through membranes) and capacitance (the ability to store charge across membranes) are crucial for understanding cellular excitability.

Completing the Circuit Model

To represent membrane potential accurately, it is depicted using a battery symbol oriented with its positive pole outside and negative inside.

A larger segment of membrane can be constructed by combining multiple elements representing various populations of ion channels (e.g., sodium, chloride).

Experimental Setup for Measuring Membrane Potential

Conducting Measurements

An experiment involves inserting a voltmeter into a neuron to measure resting membrane potential directly.

Current Injection and Membrane Potential Dynamics

Introduction to Current Injection

The experiment involves placing a current generator in the setup to analyze its effects on cellular dynamics.

Stimulating the Cell with Negative Charges

Electrodes are used to stimulate the cell by injecting negative charges, making the interior of the cell more negative compared to the exterior.

This results in hyperpolarization of the membrane potential, which is recorded alongside the injected current.

Observing Membrane Responses

Upon applying a square pulse of incoming current, each pulse further hyperpolarizes the membrane until the generator is turned off, returning it to resting potential.

Increasing stimulus intensity leads to greater hyperpolarization; however, once stimulation ceases, potential returns to resting levels.

Relationship Between Current and Voltage

A linear relationship exists between injected current and voltage response; this behavior suggests that under certain conditions, cells act like resistors.

Switching Current Direction: Positive Charge Injection

The experiment shifts focus by changing current direction and injecting positive charges (outgoing current), leading to depolarization of membrane potential.

As stimulus intensity increases again, responses become more pronounced but eventually lead to uncontrolled spikes in membrane potential.

Action Potentials and Their Characteristics

The transition from passive responses (hyperpolarization/depolarization) to active responses (action potentials) is highlighted as a key observation.

It’s noted that responses differ significantly based on whether currents are incoming or outgoing; action potentials represent an active response beyond passive limits.

Analyzing Voltage Response Shapes

The shapes of voltage responses during hyperpolarization and depolarization resemble square waveforms but exhibit delays due to cellular properties.

Time Constants in Membrane Response

The observed delay in reaching maximum polarization indicates that cellular membranes behave like resistors and capacitors connected in parallel.

A time constant (tau), representing how quickly a membrane responds to stimuli, can be calculated using resistance and capacitance values.

Conclusion on Membrane Dynamics

Understanding these dynamics helps quantify how long it takes for a cell's membrane potential reaches 63% of its maximum value after stimulation.

Understanding Membrane Potential Dynamics

The Concept of Time Constants in Membrane Potential

The time taken to reach 63% of the maximum membrane potential is discussed, highlighting the exponential relaxation of the membrane back to its resting potential after stimulus cessation.

An equation representing changes in potential at both the beginning and end of a pulse is introduced, emphasizing that this will be available for review in a PDF format.

The time constant's dependency on cellular properties is noted, indicating that different cell types exhibit varying time constants which are crucial for synaptic integration.

Synaptic Integration and Neuronal Response

Two neurons with distinct time constants (1 ms and 10 ms) are presented, illustrating how they respond to action potentials arriving at the same frequency.

A chemical synapse mechanism is explained where neurotransmitter release does not directly trigger an action potential but instead causes passive changes in membrane potential.

Importance of Time Constants in Neuronal Activity

The significance of time constants is further elaborated; a neuron with a smaller tau responds more quickly to stimuli but also relaxes faster compared to one with a larger tau.

This difference allows neurons with longer time constants to accumulate depolarization from successive stimuli without sufficient relaxation, potentially reaching threshold for action potentials.

Temporal Summation Phenomenon

The concept of temporal summation is introduced, demonstrating how repeated stimulation can lead to increased depolarization if relaxation does not occur between stimuli.

Measuring Changes in Membrane Potential

An experimental setup involving current injection into muscle fibers illustrates how membrane potential changes can be measured along the fiber length using voltmeters.

It’s noted that injected current leads to an exponential decay in membrane potential over distance due to finite resistance, emphasizing that resistance affects current flow significantly.

Understanding Membrane Potential and Space Constant

Propagation of Voltage Changes

The distance at which a voltage change propagates can be quantified, specifically where the voltage reaches 37% of its maximum value. This is represented graphically as lambda (λ) for both directions.

Resistance Calculations

The square root of the ratio between membrane resistance and total resistance (intracellular plus extracellular) is crucial. Many texts simplify this by focusing on the membrane resistance alone.

Impact of Space Constant on Membrane Potential

A higher space constant (λ) indicates better preservation of membrane potential over distance. For example, an axon with a larger λ retains its potential more effectively than one with a smaller λ.

Evolutionary Adaptations in Organisms

Over time, organisms have evolved to maximize their space constant; strategies include increasing intracellular diameter to reduce resistance or developing myelin sheaths that significantly enhance membrane resistance and thus increase λ.

Action Potentials and Signal Summation

In neurons, passive signals must reach specific regions (like the trigger zone) to generate action potentials effectively. Cells with higher space constants are more likely to sum these signals successfully compared to those with lower constants, which lose voltage rapidly. This phenomenon is known as spatial summation.

Electrical Analogies in Neuronal Function

Representation of Ion Channels

An electrical analogy illustrates various ion populations (e.g., sodium, potassium, chloride), showing how equilibrium potentials differ based on ion concentration gradients across membranes. These channels are depicted as resistances in this model.

Conductance vs Resistance

Instead of using "resistance," it’s often more accurate to refer to "conductance," which relates directly to permeability through the membrane for specific ions—higher conductance means greater ease for ions to pass through the membrane.

Driving Force for Ion Movement

The driving force behind ion movement across membranes is determined by the difference between the membrane potential and each ion's equilibrium potential, emphasizing the importance of knowing these values for understanding cellular behavior during action potentials.

Equilibrium Potential and Membrane Dynamics

Understanding Equilibrium Potential

The equilibrium potential is represented using Ohm's law, where current equals the difference in potential over resistance. This can also be expressed with conductance: current equals the difference in potential multiplied by conductance.

Potassium and Sodium Currents

For potassium, the current is calculated as the difference between membrane potential and potassium equilibrium potential, multiplied by potassium conductance. Similar calculations apply for sodium and chloride currents.

Chloride Equilibrium Condition

Chloride's equilibrium condition indicates that its driving force is zero when the membrane potential matches its equilibrium potential of approximately -90 mV, suggesting no significant movement of chloride ions at rest.

Goldman Equation Overview

The Goldman equation describes membrane potential based on ion concentrations and permeabilities, incorporating factors like gas constant, temperature, valence, sodium concentration (extracellular/intracellular), potassium concentration (extracellular/intracellular), and chloride concentration (intracellular/extracellular).

Simplifying to Sodium and Potassium

When considering a stable resting state where chloride is at equilibrium, the Goldman equation simplifies to focus primarily on sodium and potassium dynamics as their permeabilities change significantly during action potentials.

Impact of Increased Sodium Conductance

If sodium conductance increases significantly compared to potassium conductance (which may be considered negligible), the membrane potential approaches sodium's equilibrium potential due to altered ionic permeability ratios.

Electrical Perspective on Membrane Potential

In a resting state with constant membrane potential, sodium and potassium currents are equal but opposite; thus their sum must equal zero for stability in membrane voltage conditions. This leads to an equation relating these currents directly to their respective equilibrium potentials.

Final Reduction of Goldman Equation

By assuming negligible potassium conductance while focusing on increased sodium conductance, we arrive at a simplified expression indicating that under such conditions, the membrane potential closely aligns with sodium’s equilibrium value. This reflects cellular behavior during action potentials as well as resting states.

Action Potential Response Description

The discussion transitions into describing active responses such as action potentials through graphical representation showing changes in voltage over time from resting state through depolarization phases marked by specific artifacts indicative of action potentials occurring within cells.

What is the Stimulus Factor and Action Potential?

Understanding Action Potentials

The action potential begins with membrane depolarization, reaching a peak before decreasing back to resting potential, followed by hyperpolarization.

The phases of an action potential include depolarization, repolarization, and hyperpolarization, lasting between 1 to 2 milliseconds.

Membrane potential changes are driven by ion currents across the membrane.

Mechanism of Depolarization

To trigger an action potential, a threshold membrane potential must be reached by opening sufficient sodium channels.

Sodium ions (Na+) flow into the cell due to their higher concentration outside compared to inside; this influx causes depolarization.

The threshold for action potentials correlates with the number of sodium channels that need activation.

Regenerative Process of Action Potential

A small stimulus opens a few sodium channels but may not generate an action potential if it doesn't reach the threshold.

Once the threshold is reached, more sodium channels open in a regenerative manner leading to rapid depolarization.

Increased sodium conductance results in further depolarization as Na+ enters the cell.

Approaching Equilibrium Potentials

As Na+ enters during depolarization, the membrane potential approaches its equilibrium but does not fully reach it due to several factors.

The driving force for Na+ decreases as membrane potential nears equilibrium; thus, less current flows over time.

Inactivation of Sodium Channels

Sodium channels are voltage-gated and quickly enter an inactive state after opening, ceasing current flow which prevents reaching full equilibrium.

This inactivation contributes to why the peak does not reach equilibrium levels.

Role of Potassium Channels in Repolarization

As sodium channels close and potassium (K+) channels begin to open slowly, K+ exits the cell contributing to repolarization.

K+ outflow makes the interior more negative again; however, it can lead to hyperpolarization beyond resting levels.

Hyperpolarization Explained

After K+ exits during repolarization, membrane potential approaches K+'s equilibrium but does not touch it before returning to resting state.

The kinetics of both Na+ and K+ channels influence how quickly these processes occur during an action potential.

Understanding Action Potentials and Ion Channel Kinetics

Kinetics of Potassium Channels

The kinetics of potassium channels is notably slower compared to sodium channels, resulting in prolonged opening times. This extended duration allows more potassium ions to flow through the channels.

As a consequence of this slow kinetics, the membrane potential becomes more negative than the resting potential due to increased potassium conductance.

Sodium Channel Activation and Inactivation

Sodium channels transition from a closed state to an open state upon activation, then move into an inactive state. This sequence is crucial for understanding action potentials.

After an action potential, if another stimulus occurs while most sodium channels are inactivated, it cannot trigger a new action potential. This highlights the importance of channel states in neuronal firing.

Refractory Period

The time during which a threshold stimulus cannot generate another action potential is known as the absolute refractory period. During this phase, most sodium channels remain inactive.

As time progresses post-action potential, some sodium channels transition back from their inactive state to a closed state, allowing for future excitability once enough have reset.