Physiology module 2 async flashcards
The Basics of Membrane Potentials
Introduction to nerve and muscle physiology: These notes provide a fundamental understanding of how electrical signals are generated and transmitted in excitable tissues, which is crucial for comprehending bodily functions like thought, movement, and sensation.
Overview of membrane potentials.
Key concepts: resting membrane potentials (the baseline electrical state of a cell at rest) and action potentials (rapid, transient changes in membrane potential that allow for communication).
Unit Objectives
Recap the difference between diffusion potential and equilibrium potential.
Membrane Potentials
Diffusion Potential
Defined as the potential difference generated across the membrane when an ion moves down its concentration gradient from an area of high concentration to an area of lower concentration.
This ion movement requires the cell membrane to be permeable to that specific ion, typically through ion channels.
As charged ions flow across the membrane, they generate an electrical current, which creates a potential difference (voltage) across the membrane.
Equilibrium Potential
Refers to the specific electrical potential difference across the membrane that exactly opposes the net diffusion of a particular ion down its concentration gradient.
At equilibrium, the electrical force pulling the ion in one direction is equal and opposite to the chemical force pushing it in the other direction, resulting in no net movement of that ion across the membrane.
The Nernst equation is used to calculate the equilibrium potential
Example Scenario
Consider a cell with:
Intracellular: High concentration of Potassium (K+).
Extracellular: High concentration of Sodium (Na+).
If the membrane is permeable only to K+, K+ will diffuse from inside to outside, carrying positive charge out of the cell. This creates a current and leads to a negative charge accumulating inside the cell relative to the outside.
Eventually, this outward chemical force for K+ diffusion is balanced by an inward electrical force (due to the negative interior), at which point equilibrium is reached, resulting in a measurable equilibrium potential (K+ equilibrium potential being negative).
Important Values
The equilibrium potential for Potassium (K+) is approximately -94 \text{ mV} \textbf{ (closer to the resting membrane potential)} because the cell membrane is much more permeable to K+ at rest.
The equilibrium potential for Sodium (Na+) is approximately +61 \text{ mV} \textbf{ (further from the resting membrane potential)} due to its higher extracellular concentration and lower resting permeability.
Membrane Permeability
The resting membrane potential is influenced significantly by potassium permeability.
The membrane is far more permeable to K+ than to Na+ at rest, primarily due to the presence of numerous potassium leak channels that are open and allow K+ to slowly diffuse out of the cell.
Sodium channels do not contribute to resting potential as significantly because most voltage-gated sodium channels are closed at rest, and there are far fewer sodium leak channels compared to potassium leak channels.
Contribution of Sodium-Potassium ATPase Pump
This active transport pump plays a critical role in maintaining the ion gradients essential for membrane potential.
It actively pumps three Sodium (Na+) ions out of the cell for every two Potassium (K+) ions brought into the cell, against their respective concentration gradients.
This unequal movement of charges (net loss of one positive charge per cycle) makes the pump electrogenic, contributing a small but significant direct negative charge (about -4 \text{ mV}) to the resting membrane potential. More importantly, it maintains the concentration gradients that drive the diffusion potentials.
Resting Membrane Potential
Continuing the discussion from membrane potentials, the resting membrane potential (RMP) is the steady-state voltage across the cell membrane of a neuron or muscle cell when it is not actively signaling.
Resting potential is primarily influenced by the movement of K+ and Na+ ions across the membrane, guided by their concentration gradients and the relative permeability of the membrane to each ion.
Key Mechanisms
K+ Movement: Higher concentration inside the cell; the slow, continuous loss of positive K+ ions through leak channels leads to negativity inside the cell.
Na+ Movement: Higher concentration outside the cell; the slight, continuous gain of positive Na+ ions through a few leak channels leads to marginal positivity inside the cell, but this effect is minimal compared to K+ efflux.
Isolated Scenarios
K+ Only Scenario: If the membrane were only permeable to K+,
K+ would diffuse out until the interior developed a negative charge sufficient to pull K+ back in, reaching electrochemical equilibrium.
This would lead to a negative resting potential, essentially equal to the K+ equilibrium potential.
Equilibrium potential for K+ calculated as approximately -94 \text{ mV}.
Na+ Only Scenario: If the membrane were only permeable to Na+,
Na+ would diffuse into the cell until the interior developed a positive charge sufficient to push Na+ back out.
This would lead to a positive resting potential, essentially equal to the Na+ equilibrium potential.
Equilibrium potential for Na+ calculated as approximately +61 \text{ mV}.
Comparison of Potentials
Resting membrane potential typically varies from -90 \text{ mV} to -70 \text{ mV} in different excitable cells.
Why is the RMP closer to K+ equilibrium?
The primary reason is that the cell membrane at rest is vastly more permeable to K+ than to Na+ due to a higher number of open K+ leak channels. Therefore, the resting potential is much more heavily weighted towards K+'s equilibrium potential.
The Goldman-Hodgkin-Katz equation (GHK equation) provides a more accurate calculation by considering the relative permeabilities of multiple ions.
Permeability Changes
Increased permeability to K+ (e.g., more K+ leak channels opening or delayed rectifier K+ channels opening) causes the resting potential to become more negative, approaching -94 \text{ mV} (hyperpolarization).
Increased permeability to Na+ (e.g., opening of voltage-gated Na+ channels) shifts the resting potential towards +61 \text{ mV} (depolarization).
The Action Potential
Action potential essentials in nerve and muscle physiology: Action potentials are rapid, transient, and self-propagating electrical signals that transmit information over long distances in the nervous system and initiate contraction in muscle cells.
Introduction to the Action Potential
Action potentials are triggered by sudden, temporary changes in the permeability of the cell membrane to ions, primarily Na+ and K+, which are mediated by voltage-gated ion channels.
Distinguished from resting potentials by their all-or-none characteristics: once the threshold is reached, an action potential of a consistent amplitude is generated, regardless of the strength of the suprathreshold stimulus.
Key Definitions
Depolarization: The membrane potential becomes less negative (or more positive) than the resting potential. This is typically caused by an influx of positive ions, such as Na+, into the cell.
Hyperpolarization: The membrane potential becomes more negative than the resting potential. This is often caused by an efflux of positive ions (e.g., K+) or an influx of negative ions (e.g., Cl-) out of the cell.
Repolarization: The process by which the membrane potential returns toward the resting membrane potential after a depolarization event. This is usually due to the efflux of K+ ions and inactivation of Na+ channels.
Action Potential Generation
Threshold potential: A critical level of membrane potential that must be reached for an action potential to be triggered. Below this threshold, depolarization will not result in an action potential.
Typically around -55 \text{ mV} to -50 \text{ mV} for many neurons. At threshold, a sufficient number of voltage-gated Na+ channels open to initiate a regenerative cycle of depolarization.
Characteristic Phases of Action Potential
Resting State: The membrane is at its resting potential (e.g., -70 \text{ mV}), with voltage-gated Na+ and K+ channels closed, but K+ leak channels are open.
Stimulus (Graded Potential): A depolarizing stimulus causes the membrane potential to rise from rest. If this stimulus reaches the threshold potential,
Depolarization (Rising Phase): A rapid and dramatic increase in positive membrane potential occurs as voltage-gated Na+ channels open, leading to a massive influx of Na+ into the cell. This drives the membrane potential towards the Na+ equilibrium potential (+61 \text{ mV}).
Overshoot: The membrane potential briefly reverses polarity, becoming positive inside (e.g., +30 \text{ mV} to +50 \text{ mV}) because of the continued Na+ influx.
Repolarization (Falling Phase): Voltage-gated Na+ channels inactivate (close and lock), stopping Na+ influx. Simultaneously, voltage-gated K+ channels (delayed rectifier K+ channels) begin to open, facilitating the efflux of K+ out of the cell. This outflow of positive charge rapidly brings the membrane potential back towards the resting state.
Afterhyperpolarization (Undershoot): Often, the membrane potential becomes even more negative than the resting potential temporarily (e.g., -80 \text{ mV} to -90 \text{ mV}) because the voltage-gated K+ channels are slow to close, allowing for continued K+ efflux. This phase is important for setting the refractory period.
Properties of Action Potentials
Action potentials do not summate; rather, once fired, they produce a maximal response. They are constant in amplitude regardless of stimulus strength (above threshold), following the all-or-none principle.
Continuous propagation down the axon without degradation (conducted without decrement): The action potential regenerates itself at each point along the membrane, ensuring that its amplitude remains constant as it travels.
Factors Affecting Conduction Velocity
Larger axon diameter: Enhances speed by reducing the internal resistance to local current flow, allowing depolarization to spread faster.
Myelinated fibers:
Conduct action potentials much faster than unmyelinated fibers. Myelin acts as an electrical insulator.
Conduction occurs via saltatory conduction, where the action potential "jumps" from one Node of Ranvier (unmyelinated gaps) to the next, regenerating only at these nodes. This significantly increases conduction speed and conserves energy.
Voltage-Gated Ion Channels
Sodium channels have two gates:
An activation gate that opens rapidly upon depolarization, allowing Na+ influx.
An inactivation gate that closes slowly after activation, blocking further Na+ influx and contributing to the refractory period.
Potassium channels typically have only one gate that opens slowly upon depolarization, facilitating K+ efflux and repolarization/hyperpolarization.
Changes in permeability during an action potential primarily involve rapid sodium influx (depolarization) followed by slower potassium efflux (repolarization).
Clinical Considerations
Local Anesthetics: Drugs like lidocaine work by binding to and inhibiting the voltage-gated sodium channels, preventing their activation and thus blocking the initiation and propagation of action potentials in sensory nerves. This results in a loss of sensation.
Demyelinating Diseases: Conditions such as multiple sclerosis (MS) involve the destruction of the myelin sheath around axons in the central nervous system. This demyelination severely impairs action potential propagation, slows conduction velocity, and can lead to complete conduction block, resulting in neurological deficits.
Muscle Contraction
Skeletal muscle structure and function: Skeletal muscles are voluntary muscles responsible for movement, maintaining posture, and generating heat.
Four main classes of muscle cells:
Skeletal muscle: Striated, voluntary, multinucleated; responsible for body movement.
Cardiac muscle: Striated, involuntary, branched, usually uninucleated; found in the heart.
Smooth muscle: Non-striated, involuntary, uninucleated; found in walls of internal organs and blood vessels.
Myoepithelial cells: Specialized epithelial cells that contract to expel secretions from glands.
Muscle Structure
Organized from whole muscles to individual sarcomeres, which are the fundamental contractile units.
Sarcomere Components:
Z-disc (or Z-line): Marks the boundaries of sarcomeres; anchors thin (actin) filaments.
Actin (thin) filaments: Composed primarily of globular (G-actin) molecules polymerized into filamentous (F-actin) strands. They have binding sites for myosin heads.
Myosin (thick) filaments: Composed of multiple myosin II molecules, each with a head (containing an actin-binding site and an ATPase site) and a tail. The heads form cross-bridges with actin.
A-band: The dark band, representing the full length of the thick (myosin) filaments, includes overlap with thin filaments.
I-band: The light band, containing only thin (actin) filaments and the Z-disc.
H-zone: A lighter region in the center of the A-band, containing only thick (myosin) filaments.
M-line: A dark line in the center of the H-zone, composed of proteins that anchor the thick filaments.
Muscle Contraction Mechanism
Sliding Filament Theory: The most widely accepted mechanism of muscle contraction.
During contraction, the myosin heads bind to actin filaments, forming cross-bridges.
Myosin heads then perform a "power stroke," pulling the thin (actin) filaments inward toward the center of the sarcomere.
This shortens the sarcomere, bringing the Z-discs closer together, without the filaments themselves changing length. The I-bands and H-zone shorten, while the A-band length remains constant.
This process is cyclical and requires ATP for detachment of myosin heads from actin and for re-cocking the myosin heads for another power stroke.
Roles of Actin and Myosin
Actin: Forms the structural backbone of the thin filaments; contains the binding sites for myosin heads, essential for the cross-bridge cycle. Also involved in cell locomotion and intracellular transport.
Myosin II: The primary motor protein in muscle cells. Its "head" region has both ATPase activity (hydrolyzes ATP for energy) and an actin-binding site. The conformational changes in the myosin head during ATP hydrolysis drive the pulling action on actin filaments, critical for muscle contraction.
Accessory Proteins
In addition to actin and myosin, several accessory proteins play vital roles in muscle structure and function:
Tropomyosin: A regulatory protein that wraps around actin filaments, blocking myosin-binding sites on actin in a resting muscle. Calcium binding to troponin moves tropomyosin, exposing these sites.
Troponin: A complex of three proteins (TnC, TnI, TnT) that binds to actin and tropomyosin, and critically, TnC binds calcium ions, initiating the conformational change that uncovers myosin-binding sites.
Alpha-actinin: A protein that anchors actin filaments to the Z-disc.
Titin: A large, elastic protein that extends from the Z-disc to the M-line, providing passive elasticity and helping to maintain the structural integrity of the sarcomere.
Nebulin: An inelastic protein associated with actin filaments, helping to regulate their length.
Neurotransmission at the Neuromuscular Junction
This is the specialized synapse where a motor neuron communicates with a muscle fiber to initiate contraction.
Steps in neuromuscular signaling:
An action potential (AP) arrives at the axon terminal of the motor neuron.
This depolarizes the terminal, opening voltage-gated Ca2+ channels.
Ca2+ influx into the terminal triggers the release of the neurotransmitter acetylcholine (ACh) into the synaptic cleft.
ACh diffuses across the cleft and binds to nicotinic acetylcholine receptors on the muscle fiber's motor end plate.
Binding of ACh opens ligand-gated ion channels, leading to a local depolarization called the end-plate potential (EPP).
If the EPP reaches threshold, it triggers a muscle action potential that propagates along the muscle fiber membrane and into the T-tubules.
The muscle AP in the T-tubules activates dihydropyridine receptors (DHPRs), which are mechanically coupled to ryanodine receptors (RyRs) on the sarcoplasmic reticulum (SR).
Activation of RyRs causes a massive release of Ca2+ from the SR into the muscle sarcoplasm. This calcium influx is the immediate trigger for muscle contraction.
Summary of Key Processes
Excitation-Contraction Coupling: The entire sequence of events from the action potential propagating along the muscle fiber to the initiation of muscle contraction by the binding of calcium to troponin.
This intricate process links the electrical signal from the nerve fiber to the mechanical event of muscle contraction, involving the release of Ca2+ from the sarcoplasmic reticulum, its binding to troponin, the consequent movement of tropomyosin, and the cyclical interaction between myosin heads and actin filaments.
Muscle Mechanics - Force Relationships
Length-Tension Relationship
This describes how the amount of isometric (constant length) force a muscle can generate is dependent on its initial resting length.
There's an optimal sarcomere length at which the muscle can produce maximal tension, typically when there is an optimal overlap between actin and myosin filaments, allowing for the greatest number of cross-bridges to form.
If the sarcomere is significantly stretched or shortened from this optimal length, the number of potential cross-bridge formations decreases, leading to reduced force generation.
Force-Velocity Relationship
This relationship describes how the velocity of muscle shortening (contraction speed) is inversely proportional to the load (force) opposes it.
Heavier loads lead to slower contractions, until at maximum load (isometric contraction), the velocity becomes zero. Conversely, with very light loads, the muscle contracts at its maximal velocity.
This is because a heavier load requires more time for myosin heads to attach, exert force, and detach, thus slowing the overall cycling rate of cross-bridges.
Muscle Fiber Types
Muscle fibers are categorized based on their speed of contraction and their primary metabolic pathway for ATP production:
Type I (Slow Oxidative): Slow contraction speed, high fatigue resistance, relies primarily on aerobic respiration. Rich in mitochondria, myoglobin (red color), and capillaries. Ideal for sustained, low-intensity activities (e.g., posture).
Type IIa (Fast Oxidative-Glycolytic): Intermediate contraction speed and fatigue resistance. Uses both aerobic and anaerobic metabolism. More powerful than Type I, used for activities requiring moderate bursts of power.
Type IIb/IIx (Fast Glycolytic): Fast contraction speed, low fatigue resistance, relies primarily on anaerobic glycolysis. Low in mitochondria and myoglobin (white color). Generates very high force but for short durations (e.g., sprinting, heavy lifting).
Motor Units
A motor unit is defined as a single motor neuron and all the muscle fibers (of the same type) that it innervates.
When a motor neuron fires an action potential, all muscle fibers within its motor unit contract simultaneously.
Size principle: States that smaller motor units (innervating fewer, smaller muscle fibers, typically Type I) are recruited first for muscle contraction. As more force is required, progressively larger motor units (innervating more, larger muscle fibers, typically Type IIa then IIb) are recruited. This allows for precise control of muscle tension and efficient energy use.
Summary
Muscle health and performance are significantly influenced by proper training, consistent use, and various physiological adaptations.
These adaptations include hypertrophy (increase in muscle fiber size due to increased myofibrils, leading to greater strength) and atrophy (decrease in muscle fiber size due to disuse or disease, leading to weakness).
Regular physical activity and nutrition are crucial for maintaining optimal muscle function and preventing muscle deterioration.