Cell Membranes: Composition, Purpose, Permeability

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Questions and Answers

Given the inherent asymmetry of the plasma membrane, which of the following statements best encapsulates the functional consequence of this structural arrangement in the context of cellular signaling?

  • It facilitates the symmetrical presentation of glycosylated moieties, optimizing cell-cell adhesion and recognition processes equally on all cellular surfaces.
  • It modulates the uniform distribution of membrane-bound enzymes, thereby ensuring consistent catalytic activity irrespective of cellular location.
  • It equalizes the electrochemical gradient across the membrane, promoting uniform ion flux and mitigating polarized cellular responses.
  • It allows for the compartmentalization of signal transduction pathways, enabling differential responses to stimuli based on receptor localization and downstream effector availability. (correct)

Considering the glycocalyx's role in cellular interaction and the implications of its negative charge, which scenarios would most likely be affected by enzymatic removal of the glycocalyx?

  • Enhanced non-specific cell adhesion and increased endocytosis.
  • Reduced cell-cell repulsion and attenuated receptor-ligand affinity. (correct)
  • Diminished phagocytosis and increased exocytosis rates.
  • Unimpeded cell migration and accelerated immune recognition.

In the context of Fick's Law of Diffusion, if a novel synthetic lipid were engineered to increase membrane thickness by an order of magnitude while simultaneously reducing lipid solubility for a specific molecule by half, how would the diffusion rate of that molecule be affected, assuming all other variables remain constant?

  • The diffusion rate would increase by approximately twofold.
  • The diffusion rate would decrease by approximately fivefold.
  • The diffusion rate would decrease by approximately twentyfold. (correct)
  • The diffusion rate would remain unchanged due to compensatory effects.

Given the role of cholesterol in modulating membrane fluidity, how would a cell membrane respond to a sudden and drastic decrease in temperature if it were engineered to lack cholesterol?

<p>The membrane would exhibit increased rigidity and phase transition, potentially leading to impaired function. (C)</p> Signup and view all the answers

Considering the structural and functional diversity of membrane proteins, which biophysical method would be most appropriate for determining the dynamic changes in protein conformation and oligomeric state within a native cell membrane environment in situ?

<p>Förster Resonance Energy Transfer (FRET) microscopy, due to its sensitivity to distance changes between fluorescently labeled proteins in living cells. (B)</p> Signup and view all the answers

In the context of membrane transport mechanisms, if a researcher discovers a novel integral membrane protein that facilitates the movement of a specific molecule across the plasma membrane without ATP hydrolysis, yet the transport rate is significantly higher than predicted by Fick's Law alone, how would you classify this protein's transport mechanism?

<p>Facilitated Diffusion via a Carrier Protein, due to its protein-mediated, energy-independent, and saturable transport characteristics. (C)</p> Signup and view all the answers

Given a scenario where a cell's membrane potential is experimentally clamped at 0 mV, what impact would this have on the electrochemical gradient and subsequent movement of ions across the membrane?

<p>It would abolish only the electrical component of the electrochemical gradient, while preserving the chemical component, potentially leading to ion flux based solely on concentration differences. (A)</p> Signup and view all the answers

How would artificially increasing the expression of aquaporin channels in a cell membrane affect the cell's response to osmotic stress induced by exposure to a hypertonic solution?

<p>It would exacerbate cellular shrinkage due to accelerated water efflux down the osmotic gradient. (A)</p> Signup and view all the answers

Considering the mechanism of the $Na^+/K^+$ ATPase pump, predict the immediate consequences of selectively inhibiting its dephosphorylation step using a non-hydrolyzable phosphate analog?

<p>The pump would become locked in the $E_2-P$ conformation, preventing $K^+$ binding and subsequent ion translocation. (D)</p> Signup and view all the answers

If a cell were engineered to express a constitutively active (always 'on') G protein-coupled receptor (GPCR) that signals via the cAMP pathway, what long-term cellular adaptations would most likely occur to counteract the chronic overstimulation?

<p>Upregulation of phosphodiesterase (PDE) expression, downregulation of adenylyl cyclase expression and increased receptor endocytosis. (A)</p> Signup and view all the answers

In the context of receptor-mediated endocytosis, if a cell were genetically modified to lack functional clathrin protein, predict the most immediate downstream effect on cellular uptake of transferrin.

<p>Transferrin receptors would cluster diffusely on the cell surface, but the initiation of endocytic vesicles would be impaired, significantly reducing transferrin uptake. (A)</p> Signup and view all the answers

A researcher discovers a novel ligand that binds to a cell surface receptor. Upon binding, the receptor activates a cascade that ultimately leads to increased gene expression in the nucleus. Knowing that the ligand itself does not enter the cell, which of the following mechanisms would most accurately describe the signal transduction pathway involved?

<p>The receptor activates a series of intracellular second messengers that amplify the signal and ultimately regulate transcription factors. (C)</p> Signup and view all the answers

In a hypothetical scenario, a researcher synthesizes a novel amphipathic molecule that spontaneously inserts into cell membranes, disrupting lipid packing and creating 'leaky' patches. How would this affect ion gradients and cellular homeostasis?

<p>Intracellular ion concentrations would equilibrate with the extracellular environment, disrupting cellular processes. (D)</p> Signup and view all the answers

Given that lipid rafts are enriched in cholesterol and sphingolipids, what biophysical technique would be most suitable to evaluate the lateral diffusion and dynamic behavior of a GPI-anchored protein within these specialized membrane domains?

<p>Fluorescence Recovery After Photobleaching (FRAP) microscopy, for measuring the rate of protein diffusion within the membrane. (B)</p> Signup and view all the answers

If a researcher discovers that a particular genetic mutation results in the production of a transmembrane protein with a significantly shortened intracellular domain, how might this affect signal transduction processes initiated by that receptor?

<p>It would disrupt interactions with intracellular signaling molecules, potentially leading to impaired or altered downstream responses. (B)</p> Signup and view all the answers

Considering the differences between channel and carrier proteins, what would be the predicted outcome of introducing a mutation that causes a carrier protein to form a continuous, water-filled pore through the membrane?

<p>The protein would lose its specificity and selectivity, acting as a channel for various molecules. (B)</p> Signup and view all the answers

If a lipid-soluble signaling molecule were designed to have a high affinity for both membrane and intracellular receptors, which cellular responses would be expected?

<p>A combination of rapid changes in membrane excitability and long-term changes in protein synthesis. (A)</p> Signup and view all the answers

How would a point mutation in the ligand-binding domain of a receptor tyrosine kinase (RTK) that prevents its dimerization affect downstream signaling pathways?

<p>It would prevent receptor autophosphorylation and subsequent activation of downstream signaling cascades. (D)</p> Signup and view all the answers

Given the complexity of cellular signaling networks, what experimental approach would be most effective in elucidating the specific interactions and temporal dynamics of protein complexes formed during signal transduction events?

<p>Co-immunoprecipitation followed by mass spectrometry, due to its capacity identify interacting proteins under specific conditions. (A)</p> Signup and view all the answers

How does the stoichiometry of ion binding sites on a ligand-gated ion channel affect the channel's response to varying concentrations of its ligand?

<p>A higher stoichiometry results in a lower EC50, indicating increased sensitivity to the ligand. (A)</p> Signup and view all the answers

If a cell were treated with a drug that selectively disrupts the interaction between G protein subunits and the receptor, which downstream signaling events would be most immediately affected?

<p>Activation of adenylyl cyclase and subsequent cAMP production. (B)</p> Signup and view all the answers

A researcher discovers a novel mutation in the gene encoding connexin proteins, resulting in the formation of gap junctions with significantly reduced pore size. How would this altered pore size most directly impact intercellular communication?

<p>It would selectively permit the exchange of small signaling molecules while blocking the transfer of larger metabolites and ions. (A)</p> Signup and view all the answers

If the extracellular concentration of $Na^+$ ions is suddenly reduced to near zero, how would this affect the secondary active transport of glucose into intestinal epithelial cells via SGLT1 transporters?

<p>Glucose transport would cease entirely due to the collapse of the $Na^+$ electrochemical gradient. (D)</p> Signup and view all the answers

If a cell were engineered to express a non-functional version of dynamin protein, what cellular process would be most directly impaired?

<p>The budding and scission of vesicles from the plasma membrane during endocytosis. (B)</p> Signup and view all the answers

In electrophysiology, how would the introduction of a non-selective cation channel (permeable to both $Na^+$ and $K^+$) into the plasma membrane of a neuron at resting membrane potential affect the membrane potential?

<p>The membrane potential would depolarize due to increased $Na^+$ influx. (B)</p> Signup and view all the answers

Given the properties of voltage-gated ion channels, how would a mutation that shifts the voltage-dependence of channel activation to more negative potentials affect neuronal excitability?

<p>It would promote spontaneous action potential firing, increasing neuronal excitability. (A)</p> Signup and view all the answers

In the scenario where intracellular chloride concentration is experimentally increased above its normal equilibrium potential in a neuron, how would the activation of GABA-A receptors affect the membrane potential?

<p>GABA-A receptor activation would cause membrane depolarization due to Cl- efflux. (A)</p> Signup and view all the answers

In the context of long-term potentiation (LTP) at glutamatergic synapses, how would selectively blocking the insertion of AMPA receptors into the postsynaptic membrane affect synaptic plasticity?

<p>It would prevent LTP by blocking the increase in postsynaptic responsiveness to glutamate. (C)</p> Signup and view all the answers

If a researcher designs a drug that selectively inhibits the activity of phosphodiesterases (PDEs) in neurons, how would this affect synaptic transmission mediated by G protein-coupled receptors (GPCRs) that signal through cAMP?

<p>It would enhance synaptic transmission by prolonging the duration of cAMP signaling. (A)</p> Signup and view all the answers

Given the complexity of membrane dynamics and cellular signaling, what theoretical framework provides the most comprehensive approach to understanding the emergent properties arising from the interactions of multiple components within the cell membrane?

<p>Systems biology and network analysis, due to their ability to model complex interactions and predict emergent behaviors. (C)</p> Signup and view all the answers

If the activity of the $Na^+/K^+$ ATPase pump were completely inhibited in a neuron, what would be the long-term consequences for the neuron's ability to maintain its resting membrane potential and generate action potentials?

<p>The neuron would gradually depolarize, eventually becoming unable to generate action potentials due to the dissipation of ion gradients. (D)</p> Signup and view all the answers

How would altering the lipid composition of a cell membrane to incorporate a higher proportion of unsaturated fatty acids affect the kinetics of integral membrane protein function, particularly those involved in signal transduction?

<p>It would increase membrane fluidity, potentially affecting protein conformation, diffusion, and interaction with other signaling molecules, thus affecting signal-transduction efficiency. (C)</p> Signup and view all the answers

Given that the phospholipid bilayer is impermeable to ions, how can the cell membrane potential change rapidly in response to a stimulus?

<p>Ions utilize integral membrane proteins, such as ion channels, to traverse the membrane. (B)</p> Signup and view all the answers

If a researcher discovers a novel compound that selectively inhibits the function of caveolin proteins, how would this affect caveolae-mediated endocytosis and potocytosis?

<p>It would impair caveolae formation and endocytosis by disrupting the structural integrity of caveolae. (A)</p> Signup and view all the answers

In the scenario where a neuron is exposed to a toxin that selectively blocks voltage-gated potassium channels, how would this affect the repolarization phase of the action potential?

<p>The repolarization phase would be prolonged or absent, leading to extended depolarization. (A)</p> Signup and view all the answers

Given the role of the ER in protein synthesis, which of the following is not correct about the RER?

<p>RER can synthesize lipids and steroids. (A)</p> Signup and view all the answers

If a hypothetical molecule with a molecular weight of 600 Daltons and a partition coefficient of 0.8 (octanol/water) is introduced into a cell, by which transport mechanism is it most likely to cross the cell membrane?

<p>Simple Diffusion (D)</p> Signup and view all the answers

Flashcards

Cell membrane

A thin, elastic structure, 7.5-10 nanometers thick, primarily composed of a sheet of lipid (fat) material, phospholipids and cholesterol, with interspersed proteins.

Phospholipids

The most abundant lipid in all membranes, forming a double layer with hydrophilic heads facing outwards and hydrophobic tails inwards.

Glycocalyx

The

Membrane Permeability

Hydrophobic molecules pass easily, hydrophilic need help.

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Passive Transport

Movement across a membrane without energy input

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Diffusion

Movement across a membrane utilizing a concentration gradient

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Simple Diffusion

Diffusion directly through lipid bilayer

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Facilitated Diffusion

Diffusion with help of with carriers/channels in membrane

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Membrane proteins

Specific proteins aiding movement across membrane

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Channel Protein

Membrane protein forms a pore for substance flow

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Gated Channels

Channels opening under specific stimulus

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Voltage-Gated Channel

Channel Opening with electrical event

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Active Transport

Energy needed to move against concentration gradient

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Carrier Proteins

A protein that pumps substances against their concentration gradients.

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Na+/K+ pump

Primary active transport enzyme

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ATP Hydrolysis

Energy required to pump 3 Na+ ions out, 2 K+ ions in.

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Co-Transport

Gradient drives other substances against their gradient

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Symport

Substances move in same direction

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Antiport

Substances move in opposite directions

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Cell Signaling

When cell membrane receptors are activated

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Endocytosis

Binding causes transport of substances into cells

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Exocytosis

A process where a cell directs the contents of secretory vesicles out of the cell membrane and into the extracellular space

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Ligand-Receptor Interaction

Water soluble

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Signal Transduction

Chemical event influencing the inner workings of the cell

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Receptor Enzyme

A signal binds to transmembrane protein on receptor region

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Ligand-Gated Channels

Membrane receptor where binding causes ion channel to open

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Membrane Potential

Electrical Charge difference

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Resting Membrane Potential

This membrane potential at rest

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Depolarization

Opening sodium channels

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Repolarization

Closing sodium channels

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Excitable Cells

Nerve cells, muscle cells

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Study Notes

Cell Membranes: Purpose

  • Cell membranes are essential to prevent cell contents from being stripped away.
  • Non-biological comparisons could be a dam, holding back water, or a fence, providing security.
  • Selective permeability is crucial to cell function.

Selective Permeability

  • Energy requirements include glucose, fatty acids, amino acids, and oxygen.
  • Signals/messages involve hormones, neurotransmitters, cytokines, and ions.
  • Waste removal includes carbon dioxide, water, and lysosomal/proteasomal breakdown products.
  • Maintaining membrane potential uses ions.
  • Osmosis/water balance involves water.

Cell Membrane Composition and Structure

  • The body is composed of over a hundred trillion cells, they work continuously like small factories.
  • Cells have miniature brains (DNA) and energy sources (mitochondria).
  • Cells are also able to communicate with one another to produce proteins and hormones.
  • It is a thin, elastic sheet of lipid material, interspersed with proteins and 7.5-10 nanometers in thickness.
  • A nanometer= 1x10-9 m.
  • Membranes that surround the nucleus and other organelles are almost identical to the cell membrane.
  • Phospholipids form a thin flexible sheet, while proteins "float" within like icebergs.
  • Carbohydrates extend out from the proteins.

Cell Membrane Components:

  • The cell membrane consists of cholesterol, phospholipids, sphingolipids, carbohydrates, and proteins.
  • Phospholipids and Sphingolipids together form a lipid bilayer, selectively barring substances between the cytosol and the external environment.
  • Carbohydrates form glycolipids and glycoproteins.
  • Glycolipids and glycoproteins have structural stability, aid cell recognition and immune response.

Lipid Bilayer

  • Plasma and organelle membranes are composed of 40-80% lipid.
  • Hydrophobic lipids have water insoluble/fat soluble fatty acids.
  • Hydrophilic lipids are polar, with water soluble/fat insoluble "heads", on the outside.
  • Phospholipids make up the most abundant lipid in all membranes.
  • Cholesterol influences the fluidity of the membrane.

Membrane Proteins

  • Float in a "sea" of membrane lipids.
  • Their amount depends on the function of the membrane.
  • Protein:lipid ratio in different membranes ranges from 1:4 to 4:1.
  • Components are asymmetrically situated in the membrane.
  • Classified according to their structure or function.

Membrane Proteins Functions

  • Types include membrane transporters, structural proteins, membrane enzymes and membrane receptors.
  • Membrane transporter proteins can be channel proteins which form channels or carrier proteins, which create membrane carriers .
  • Structural proteins anchor the cytoskeleton to the membrane.

Membrane Receptors Interactions

  • A ligand binds to to a cell membrane receptor protein.
  • A ligand-receptor complex then triggers an intracellular response.

Channel Proteins

  • They create a water-filled pore within the cell.
  • Can be classified as open or gated channels.

Carrier Proteins

  • Carrier proteins never form an open channel between the two sides of the membrane.
  • Can be classified as uniport, symport and antiport carriers.

Glycocalyx

  • The glycocalyx is an outer glycoprotein layer on the cell surface.
  • Serves as carbohydrate ("sugar") side chains of glycoproteins which act as binding sites for the extracellular matrix.
  • It provides the outside of the cell membrane surface with a negative charge and plays a key role in cell-to-cell contact and adhesion.
  • The coat functions as an outer layer and structural part of the membrane which connects to with the extracellular environment.

Membrane Dynamics

  • Import and export rely on membrane properties/structures, properties of transported molecules/substances, and energy availability.

Diffusion

  • Types include simple and facilitated diffusion.
  • There are energy and physical requirements for both.

Diffusion: Key Concepts

  • Concentration gradient and no ATP energy are required as it is passive.
  • Energy is obtained from own kinetic energy.
  • Solubility properties determine the ease with which molecules diffuse.
  • For fat-soluble, non-polar molecules, include gases and other lyophilic molecules- these dissolve in cell membrane enabling SIMPLE diffusion.
  • For water-soluble, polar molecules, such as ions and other lyophobic molecules, need membrane PROTEINS enabling FACILITATED diffusion.

Examples of Fick's Law of Simple Diffusion

  • Movement of gases across cell membranes, such as O2, CO2, and NO, are lipophilic and can therefore dissolve in cell membranes.

Facilitated Diffusion: Key Concepts

  • No ATP energy is required for this to take place.
  • Movement is concentration gradient driven.
  • Process is for dissolving molecules in cell membrane.

Facilitated Diffusion and Membrane Proteins:

  • Can function using channel proteins, via an open/leaking or gated channel.
  • Can function using carrier proteins, for example as a glucose uptake into cells.

Gated Ion Channels:

  • Gated channels are protein channels which open under certain conditions.
  • A voltage-gated channel is opened by an electrical event.
  • A ligand-gated channel is when a chemical signal opens a gated channel.

Primary Active Transport

  • Chemical energy from hydrolysis of ATP is supplied.
  • Best example is the Na+/K+ pump.
  • This enzyme (Na+/K+-ATP-ase) acts alongside a membrane carrier protein.
  • Hydrolysis of 1 ATP pumps 3 Na+ ions out of cell and 2 K+ ions into cell.
  • ATPase can act as a carrier protein to pump Na+ out of cell and K+ into cell, against concentration gradients.

Co-Transport:

  • Na+-Glucose Co-Transporter is an example.
  • Glucose has to enter epithelial cells of small intestine or proximal renal tubules against its gradient.
  • A membrane carrier protein called the Na-Glucose Co-Transporter is used for glucose uptake in these cells.

Endocytosis and Exocytosis

  • There are receptor-intracellular signal transduction cascades

Receptor-Intracellular Signal

  • Water-soluble ligands bind to cell membrane receptors.
  • Fat-soluble ligands canbind to cellular receptors (cytoplasmic and or nuclear).
  • Cell membrane receptors can be divided into: receptor-channel, receptor-enzyme, G protein-coupled receptors or integrin receptors.

Ligand and Receptors, "Lock and Key" Analogy:

  • Analogy: Ligand (key) binds to receptor (keyhole) to form Cellular Effect (ignition)
  • Ligand is a hormone, neurotransmitter, or cytokine, and the receptor is on a membrane or it’s inside of the cell.
  • Intracellularly, this is the cell’s mechanism that leads to an effect.

More Analogies:

  • Insulin binds to its perfect fit receptor, which sets an intracellular mechanism into action and leads to glucose uptake.
  • Adrenalin + B-adrenergic receptor increases heart rate
  • Acetylcholine + nicotinic receptor causes skeletal muscle contraction
  • Cortisol + GC-receptor results in gluconeogenesis.

G-Protein-Coupled Receptors

  • Ligand binds to G-protein-coupled receptor (“GPCR”), ligand-receptor complex activates a membrane protein called G-protein (“signal transducer”).
  • As a result, an amplifying enzyme might be activated, or a nearby ion channel can allow flow of ions through the channel.
  • Ligand does not enter the cell but triggers the switching on of a mechanism.
  • This involves signal transducers (G-proteins), amplifying enzymes and second messenger systems, which create an “intracellular signal transduction pathway".

Intracellular Signal Transduction

  • Signal transduction converts one form of signal into a different form.

Receptor-Enzyme Receptors

  • The receptor connects to an intracellular enzyme forming a receptor-enzyme complex.
  • Tyrosine kinase (TK) enzyme leads to activation of intracellular phosphorylation.
  • An example of insulin-receptor (found on muscle, liver and fast cells).

Ligand-Gated Ion Channels

  • Ligand-gated channels act as receptors.

Ligand-Gated Ions Channels Examples:

  • There are nicotinic acetylcholines receptors at the neuromuscular junction.
  • This receptor has 2 binding sites.
  • It’s a gated ion channel.
  • Na and K+ ions move in and out.
  • This causes depolarization of muscle cell membrane.

Fat-Soluble Ligands

  • They act in the nucleus
  • By leading the synthesis to new proteins or blocking it.

Membrane Properties: Ion distribution

  • Cells have an unequal chemical ion distribution between intracellular, interstitial and intravascular fluid compartments.
  • Resting membrane potential difference, ion channels close thereby preventing charged flow in/out of cells.

Resting Cell Membrane Potential

  • Cell membrane separates two areas (intracellular/extracellular space) with different electrical charges.
  • A potential difference develops across membrane.
  • Charged particles prevent from flowing.

Depolarization and Repolarization

  • When region of membrane depolarizes, charge becomes more positive due to influx of Na+ ions.
  • During repolarization, charge becomes more negative again as Na+ channels close.
  • K is allowed to flow out.
  • Sometimes K continues to flow out of cell until the charge on cell membrane region becomes negative.
  • Membrane can then become hyper polarized.

Action Potentials

  • An electrical messenger.
  • As Na_ channels open stream into cell, causes depolarization.
  • Stops streaming in as k streams out, causing repolarization (returning membrane back to resting).

Potassium and Sodium Pump

  • Restoration of ion balances after depolarization and repolarization.
  • The Na+ / K+ Pump.
  • Restores potassium and sodium.

Electrical Properties of Cell Membranes Recap

  • Excitable cells like nerve, skeletal and heart muscle cells have electrical properties.
  • Electrical potential differences exist between the inside and outside because of chemical/electrical disequilibrium.
  • At rest it's called "resting membrane potential". The membrane is undisturbed with closed gated ions. When you disturb, the ion changes open/close, causing dramatic movement and try to reach electrical/chemical equilibrium.
  • Opening/closing various ion channels leads to the action potential which can cause rapid impulses.
  • In nerve cells these impulses are messengers, signals that will lead with eventual neurotransmitter release.

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