Membrane Potential

Overview

• Most cells in the human body hold a membrane potential.
  • The lipid bilayer of the plasma membrane Plasma membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane (PM) insulates the inside of the cell from the outside and does not allow the free diffusion Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport. Peritoneal Dialysis and Hemodialysis of ions.
  • Selective ion channels Channels The Cell: Cell Membrane and transporters allow for increases in concentration of charged ions inside and/or outside the PM.
• Most cells have an electric potential across their PM.
  • The inside of the cell is slightly more negative than the outside.
  • In some cells, this charge can equalize or even reverse rapidly in response to stimuli.
• Types of potential
  • Resting membrane potential 
  • Equilibrium Equilibrium Occurs when tumor cells survive the initial elimination attempt These cells are not able to progress, being maintained in a state of dormancy by the adaptive immune system. In this phase, tumor immunogenicity is edited, where T cells keep selectively attacking highly immunogenic tumor cells.This attack leaves other cells with less immunogenicity to potentially develop resistance to the immune response. Cancer Immunotherapy potential 
  • Nerve action potential

Equilibrium Potential

Overview

• Also known as the reversal potential or “isoelectric state“
• Transmembrane potential voltage at which there is no net flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure of ions across a PM
  • Ions diffuse along their concentration gradient as well as to neutralize their electrical charges (e.g., negatively charged ions wish to travel toward positively charged areas).
  • May act together to push ions in 1 direction or can contrast each other

Nernst equation

Used to calculate the equilibrium Equilibrium Occurs when tumor cells survive the initial elimination attempt These cells are not able to progress, being maintained in a state of dormancy by the adaptive immune system. In this phase, tumor immunogenicity is edited, where T cells keep selectively attacking highly immunogenic tumor cells.This attack leaves other cells with less immunogenicity to potentially develop resistance to the immune response. Cancer Immunotherapy potential at a given concentration difference of a permeable ion across the cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane.

$$ V_{eq}= \left ( RT/zF \right )ln\left ( X_{o} /X_{i}\right ) $$

Veq = equilibrium Equilibrium Occurs when tumor cells survive the initial elimination attempt These cells are not able to progress, being maintained in a state of dormancy by the adaptive immune system. In this phase, tumor immunogenicity is edited, where T cells keep selectively attacking highly immunogenic tumor cells.This attack leaves other cells with less immunogenicity to potentially develop resistance to the immune response. Cancer Immunotherapy potential for the ion X
R = gas constant (8.314 joules per kelvin per mole Mole Nevi (singular nevus), also known as “moles,” are benign neoplasms of the skin. Nevus is a non-specific medical term because it encompasses both congenital and acquired lesions, hyper- and hypopigmented lesions, and raised or flat lesions. Nevus/Nevi)
T = temperature in kelvin (K = °C + 273.15)
z = charge on the ion (+1 for Na+, +2 for Ca2+, −1 for Cl−)
F = Faraday constant (96,485 Coulombs per mole Mole Nevi (singular nevus), also known as “moles,” are benign neoplasms of the skin. Nevus is a non-specific medical term because it encompasses both congenital and acquired lesions, hyper- and hypopigmented lesions, and raised or flat lesions. Nevus/Nevi)
Xi = intracellular concentration ( mM MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma)
Xo = extracellular concentration ( mM MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma)

Resting Membrane Potential

Overview

• Potential that cells have across their membranes at their baseline state
  • Excitable cells ( neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology, cardiac muscle Cardiac muscle The muscle tissue of the heart. It is composed of striated, involuntary muscle cells connected to form the contractile pump to generate blood flow. Muscle Tissue: Histology, etc ETC The electron transport chain (ETC) sends electrons through a series of proteins, which generate an electrochemical proton gradient that produces energy in the form of adenosine triphosphate (ATP). Electron Transport Chain (ETC)) return to this resting potential between action potentials
  • Non-excitable cells remain constantly at their resting potential.
• Result of the movement of several different ion species through various ion channels Channels The Cell: Cell Membrane and transporters (uniporters, cotransporters, and pumps) in the PM
• Diffusion Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport. Peritoneal Dialysis and Hemodialysis potential depends on
  • The charge of the ions (primarily Na+, K+, and Cl-)
  • The difference in concentration of ions inside vs. outside the cell
  • The permeability of the PM to the ions
• Resting membrane potentials of various tissues:
  • Neuron -70mV
  • Skeletal muscle -90mV
  • Cardiac -90mV
• Restless membrane potential
  • Unstable potential 
  • Oscillates between -60mV and -40mV 
  • Seen in pacemaker Pacemaker A device designed to stimulate, by electric impulses, contraction of the heart muscles. It may be temporary (external) or permanent (internal or internal-external). Bradyarrhythmias tissues
    • Sinoatrial (SA) node in cardiovascular system (CVS)
    • Cajal cells in GI tract
    • The pre-Bötzinger complex: a neural network in the ventrolateral brainstem that generates the respiratory rhythm

Goldman equation

The resting membrane potential can be considered the average of the equilibrium Equilibrium Occurs when tumor cells survive the initial elimination attempt These cells are not able to progress, being maintained in a state of dormancy by the adaptive immune system. In this phase, tumor immunogenicity is edited, where T cells keep selectively attacking highly immunogenic tumor cells.This attack leaves other cells with less immunogenicity to potentially develop resistance to the immune response. Cancer Immunotherapy potentials of all the ions that permeate in and out of a cell, modified by the relative permeability of a cell to those ions.

$$ E_{m}=\frac{RT}{F}ln\left ( \frac{P_{K}\left [ K^{+} \right ]_{out}+P_{Na}\left [ Na^{+} \right ]_{out}+P_{Cl}\left [ Cl^{-} \right ]_{in}}{P_{K}\left [ K^{+} \right ]_{in}+P_{Na}\left [ Na^{+} \right ]_{in}+P_{Cl}\left [ Cl^{-} \right ]_{out}} \right ) $$

E_m: membrane potential (in volts, or joules per coulomb)
P_ion: the selective permeability Selective permeability The Cell: Cell Membrane for the specified ion (in meters per second)
[ion]_out: concentration of the specified ion outside the cell (in moles Moles Primary Skin Lesions per cubic meter)
[ion]_in: intracellular concentration of the specified ion (in moles Moles Primary Skin Lesions per cubic meter)
R: the ideal gas constant (joules per kelvin per mole Mole Nevi (singular nevus), also known as “moles,” are benign neoplasms of the skin. Nevus is a non-specific medical term because it encompasses both congenital and acquired lesions, hyper- and hypopigmented lesions, and raised or flat lesions. Nevus/Nevi)
T: the temperature in kelvins
F: Faraday constant (coulombs per mole Mole Nevi (singular nevus), also known as “moles,” are benign neoplasms of the skin. Nevus is a non-specific medical term because it encompasses both congenital and acquired lesions, hyper- and hypopigmented lesions, and raised or flat lesions. Nevus/Nevi)

Action Potential

Overview

• Seen in excitable cells (primarily neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology)
• While at resting membrane potential, ion channels Channels The Cell: Cell Membrane open and lead to rapid flux of ions across the PM along their concentration gradient.
• Leads to rapid changes in voltage across the PM (depolarization)
• Changes are localized to the area around the open ion channels Channels The Cell: Cell Membrane.
• Voltage-sensitive ion channels Channels The Cell: Cell Membrane in adjacent areas open in response to the change in membrane potential, allowing ion influx.
• The potential is thus propagated over the entire surface of the cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane.

Phases of a nerve action potential

• Resting membrane potential in a neuron
  • At baseline -70mV 
  • Reflects the equilibrium Equilibrium Occurs when tumor cells survive the initial elimination attempt These cells are not able to progress, being maintained in a state of dormancy by the adaptive immune system. In this phase, tumor immunogenicity is edited, where T cells keep selectively attacking highly immunogenic tumor cells.This attack leaves other cells with less immunogenicity to potentially develop resistance to the immune response. Cancer Immunotherapy potential of K+ due to its high conductance across the PM (from inside to outside)
    • In a resting neuron: high concentration of Na+ in the extracellular fluid Extracellular fluid The fluid of the body that is outside of cells. It is the external environment for the cells. Body Fluid Compartments (ECF) and high concentration of K+ in the intracellular fluid Intracellular fluid The fluid inside cells. Body Fluid Compartments ( ICF ICF The fluid inside cells. Body Fluid Compartments)
    • K+ leak channels Channels The Cell: Cell Membrane are open while Na+ channels Channels The Cell: Cell Membrane are closed.
    • Leads to an outflow of K+ ions from inside the cell, generating the negative resting membrane potential
• Latent period Latent period The time between onset of the AP and onset of the muscle contraction (i.e., the twitch) Skeletal Muscle Contraction 
  • When a stimulus is given, a response doesn’t occur immediately. 
  • Time gap between stimulus and response 
• Upstroke of action potential or depolarization 
  • Depolarization occurs, which causes the opening of voltage-gated Na+ channels Channels The Cell: Cell Membrane
  • Leads to rapid Na+ ion influx into the cell along its concentration gradient
  • Na+ conductance > K+ conductance
  • This causes membrane potential to approach the equilibrium Equilibrium Occurs when tumor cells survive the initial elimination attempt These cells are not able to progress, being maintained in a state of dormancy by the adaptive immune system. In this phase, tumor immunogenicity is edited, where T cells keep selectively attacking highly immunogenic tumor cells.This attack leaves other cells with less immunogenicity to potentially develop resistance to the immune response. Cancer Immunotherapy potential of Na+ (+65mV).
  • Membrane potential remains positive for a brief period of time.
• Repolarization
  • Depolarization causes the following changes
    • Closes the inactivation gates of Na+ channels Channels The Cell: Cell Membrane 
    • Slowly opens K+ channels Channels The Cell: Cell Membrane, causing an increase K+ conductance more than the resting membrane potential 
  • K+ conductance > Na+ conductance, causing repolarization 
  • Repolarization occurs mainly due to K+ efflux 
• Overshoot or hyperpolarization 
  • The Na+ channel closes.
  • K+ conductance remains higher than the resting membrane potential at rest for some time.
  • The membrane potential reaches close to the equilibrium Equilibrium Occurs when tumor cells survive the initial elimination attempt These cells are not able to progress, being maintained in a state of dormancy by the adaptive immune system. In this phase, tumor immunogenicity is edited, where T cells keep selectively attacking highly immunogenic tumor cells.This attack leaves other cells with less immunogenicity to potentially develop resistance to the immune response. Cancer Immunotherapy potential of K+, which is -90mV.

Refractory periods

• Absolute refractory period
  • From firing to ⅓ of repolarization 
  • During this period, a 2nd stimulus, however large, cannot initiate another action potential.
• Relative refractory period
  • From the end of absolute refractory period until membrane potential reaches its resting level 
  • During this period, action potential can be elicited if a larger stimulus is provided.

Clinical Relevance

• Cardiac action potentials and pacemaker potential Pacemaker potential Cardiac Physiology: the cells of the heart transmit action potentials that are different from those seen in neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology. The peak phases of the action potentials last longer than those seen with neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology due to the activity of slower calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes ( Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)) channels Channels The Cell: Cell Membrane, which open and hold the action potential longer. In addition, a group of special cells in the SA node is characterized as having a pacemaker potential Pacemaker potential Cardiac Physiology. This action potential is automatically generated at the tail end of the previous, giving the process a repetitive automatic pattern that regulates the heartbeat.
• Brugada syndrome Brugada syndrome An autosomal dominant defect of cardiac conduction that is characterized by an abnormal st-segment in leads v1-v3 on the electrocardiogram resembling a right bundle-branch block; high risk of ventricular tachycardia; or ventricular fibrillation; syncopal episode; and possible sudden death. This syndrome is linked to mutations of gene encoding the cardiac sodium channel alpha subunit. Ventricular Tachycardia: a genetic condition leading to cardiac arrhythmias due to inherited mutations in the Na+ channels Channels The Cell: Cell Membrane in cardiac muscle Cardiac muscle The muscle tissue of the heart. It is composed of striated, involuntary muscle cells connected to form the contractile pump to generate blood flow. Muscle Tissue: Histology, which lead to aberrant action potential conduction, arrhythmia, and sudden cardiac arrest Cardiac arrest Cardiac arrest is the sudden, complete cessation of cardiac output with hemodynamic collapse. Patients present as pulseless, unresponsive, and apneic. Rhythms associated with cardiac arrest are ventricular fibrillation/tachycardia, asystole, or pulseless electrical activity. Cardiac Arrest. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are treated with implanted cardiac defibrillators that can detect aberrant rhythms and deliver a shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock to the heart to reset the action potential.