Cell Signalling Pathways

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Questions and Answers

How does the electrochemical gradient influence ion transport across a cell membrane, and under what conditions does passive transport occur?

The electrochemical gradient, a combination of electrical and chemical forces, determines ion transport. Passive transport occurs when this gradient favors the movement of ions across the membrane without requiring energy input.

Describe the role of the Na+/Ca2+ exchanger (NCX) in regulating intracellular calcium levels, and explain the stoichiometry of ion exchange in this process.

NCX is an antiporter that uses the sodium gradient to drive calcium efflux, removing calcium from the cell. For every calcium ion that is transported out, two sodium ions enter the cell.

Explain how the structure of voltage-gated potassium channels contributes to their function, focusing on the roles of the voltage-sensing domain and the pore domain.

The voltage-sensing domain responds to changes in membrane potential, initiating channel opening. The pore domain, formed by the last two building blocks, creates a selective pathway allowing only potassium ions to flow through the channel.

Explain how the polarity of a cell membrane (negative inside, positive outside) is established and maintained, and its significance for cellular function.

<p>It's established by the unequal distribution of ions and the activity of ion pumps such as the sodium-potassium pump. This polarization is essential for nerve impulse transmission, muscle contraction, and nutrient transport.</p> Signup and view all the answers

Discuss the role of calcium signaling in fertilization, including the mechanisms of calcium release and its downstream effects on egg activation.

<p>In fertilization, sperm stimulation triggers calcium release, causing calcium levels to spike. These spikes activate the egg, initiating developmental processes like cell division and formation of a protective barrier.</p> Signup and view all the answers

Describe how a P-type ATPase, such as the Na+/K+ pump or SERCA, utilizes phosphorylation to drive ion transport across cell membranes.

<p>P-type ATPases use phosphorylation to change their conformation. ATP phosphorylates the protein, allowing it to bind and transport ions. Dephosphorylation then returns the protein to its original state, releasing the ion on the other side of the membrane.</p> Signup and view all the answers

Compare and contrast the mechanisms of ion transport via simple diffusion, channel-mediated diffusion, and carrier-mediated transport.

<p>Simple diffusion is the movement of substances across a membrane down their concentration gradient without any assistance. Channel-mediated diffusion uses protein channels. Carrier-mediated diffusion involves a carrier protein that binds the solute and undergoes a conformational change to transport it across the membrane.</p> Signup and view all the answers

Elaborate on the role of active transport in generating and maintaining ion gradients across cellular membranes.

<p>Active transport uses energy, often in the form of ATP hydrolysis, to move ions against their concentration gradients, establishing and maintaining these gradients. Notably, the sodium-potassium pump actively transports sodium ions out of the cell and potassium ions into the cell.</p> Signup and view all the answers

Explain the concept of 'signaling' in the context of cellular biology, and provide examples of how extracellular stimuli can induce changes in cell function.

<p>Signaling is the process by which cells receive, process, and respond to external cues, like neurotransmitters or hormones. This leads to cascade of events that induce changes in cell function, such as altered gene expression or metabolic activity.</p> Signup and view all the answers

Describe the role of SERCA (Sarco/endoplasmic reticulum Ca2+-ATPase) in calcium signaling and explain how it contributes to the regulation of intracellular calcium concentrations.

<p>SERCA pumps calcium from the cytoplasm into the endoplasmic reticulum (ER) or sarcoplasmic reticulum (SR), reducing cytoplasmic calcium levels. This is crucial for ending calcium signaling events and maintaining proper calcium homeostasis within the cell.</p> Signup and view all the answers

How do ion channels contribute to nerve-to-nerve transmission (neurotransmission)? Elaborate on the process and the specific ions involved.

<p>Ion channels conduct action potentials, that propagate along the axon of a neuron. When the action potential reaches the nerve terminal, voltage-gated calcium channels open, causing an influx of calcium ions, which triggers the release of neurotransmitters.</p> Signup and view all the answers

Discuss the role of ion channels in the 'flight or fight' response, particularly in relation to adrenaline signaling.

<p>Adrenaline triggers various signaling pathways that modulate ion channel activity to prepare the body for action. For example, adrenaline can affect heart rate by influencing ion channels in cardiac cells.</p> Signup and view all the answers

How do ion channels contribute to the precise timing and spatial localization of calcium signals within a cell, and why is this important for cellular function?

<p>Ion channels allow for rapid and localized changes in ion concentrations, particularly calcium. The positioning and kinetics of calcium channels lead to highly localized 'calcium microdomains,' which can trigger specific downstream effects.</p> Signup and view all the answers

Explain the mechanism of secondary active transport, giving specific examples of how ion gradients are utilized to transport other molecules across the cell membrane.

<p>Secondary active transport uses the electrochemical gradient of one ion to drive the transport of another molecule. For example, the Na+/Ca2+ exchanger uses the sodium gradient to transport calcium ions out of the cell.</p> Signup and view all the answers

Discuss the various roles of calcium signaling in different cellular processes, providing specific examples of how calcium ions regulate exocytosis, gene transcription, and metabolism.

<p>Calcium ions act as a second messenger that triggers many different responses. In exocytosis, they induce the fusion of vesicles with the cell membrane, releasing their contents. In gene transcription, they activate transcription factors. In metabolism, they regulate enzyme activity.</p> Signup and view all the answers

Explain the role and mechanism of PMCA (Plasma Membrane Calcium ATPase) in maintaining low intracellular calcium concentrations.

<p>PMCA actively pumps calcium ions out of the cell, against their concentration gradient, using the energy from ATP hydrolysis. This helps to maintain a low concentration of calcium inside the cell, which is crucial for calcium signaling.</p> Signup and view all the answers

Describe the mechanism by which the Na+-K+ pump maintains ion gradients across the cell membrane, and discuss the consequences of its malfunction on cellular function.

<p>The Na+-K+ pump actively transports 3 Na+ ions out of the cell and 2 K+ ions into the cell, using ATP. Its malfunction can disrupt ion gradients, leading to impaired nerve and muscle function, altered cell volume, and disruption of secondary active transport.</p> Signup and view all the answers

Explain how differences in ion concentrations between the inside and outside of a cell influence the resting membrane potential, and how this potential is crucial for cell excitability and function.

<p>Ion concentrations create an electrochemical gradient across the membrane, mainly from Na+, K+, Cl- and charged proteins. The Na+/K+ pump maintains this gradient, resulting in a negative charge inside the cell. Changes in membrane potential trigger action potentials, essential for nerve and muscle function.</p> Signup and view all the answers

Describe how changes in membrane potential affect the opening and closing of voltage-gated ion channels, and discuss the significance of this process in the generation of action potentials.

<p>Changes in membrane potential cause conformational changes in voltage-gated ion channels. Depolarization opens Na+ channels, leading to Na+ influx and further depolarization, which drives the action potential. Repolarization opens K+ channels, allowing K+ efflux and restoring the resting membrane potential.</p> Signup and view all the answers

Describe how alterations in the expression or function of ion channels can lead to various diseases (channelopathies), providing specific examples of diseases linked to mutations in sodium, potassium, or calcium channels.

<p>Mutations in ion channel genes can result in channelopathies. For example, mutations in sodium channels can cause epilepsy, while potassium channel mutations can lead to cardiac arrhythmias, and calcium channel mutations can cause familial hemiplegic migraine.</p> Signup and view all the answers

Discuss the differences in ion concentrations inside and outside a typical mammalian cell, and explain how these differences are maintained.

<p>Typical mammalian cells have higher concentrations of Na+, Cl- outside the cell, and higher concentrations of K+ inside the cell. These are maintained by a combination of ion pumps, such as the Na+/K+ ATPase, and selective ion channels.</p> Signup and view all the answers

Describe the role of ion channels in processes such as exocytosis, muscle contraction, and proliferation. Be sure to include specific ions and channels involved.

<p>In exocytosis, Ca2+ channels mediate the calcium influx needed for vesicle fusion and neurotransmitter release. In muscle contraction, calcium release from the sarcoplasmic reticulum, via calcium channels, triggers muscle fiber contraction. In proliferation, ion channels such as K+ channels regulate membrane potential which is crucial in the cell cycle.</p> Signup and view all the answers

Describe ion transport mechanisms that are active versus passive. What are the energy requirements, and what direction do the ions travel?

<p>Active transport requires energy (ATP) to move ions against their concentration gradient. In contrast, passive transport follows the electrochemical gradient, moving ions without energy input through diffusion, channel-mediated, or carrier-mediated transport.</p> Signup and view all the answers

Discuss the specific structural domain requirements for the Voltage gated K+ channel and briefly explain how each domain contributes to the channels function.

<p>Voltage gated K+ channels have two main domains: (1) the voltage-sensing domain and (2) the pore domain. The voltage-sensing domain responds to changes in membrane potential, initiating channel opening. Then the pore domain, creates a selective pathway allowing only potassium ions to flow through the channel.</p> Signup and view all the answers

Describe the role of a stimulus on reactions such as exocytosis, contraction, and metabolism. How does the stimulus change the normal rate of these processes?

<p>A stimulus triggers various signaling pathways that modulate processes. Exocytosis and contractions speed up and begin, while metabolism increases in pace as well. Other modifications such as gene transcription, fertilization, and hyper trophy take longer and a stronger stimuli to produce.</p> Signup and view all the answers

How are ion gradients generated, and what role does ATP hydrolysis play in this process?

<p>Ion gradients are generated by the active transport of ions across the cell membrane. This process often involves ATP hydrolysis, which provides the energy needed to move ions against their concentration gradients.</p> Signup and view all the answers

How does calcium signaling interact with gene transcription to change the expression profile of a cell?

<p>Calcium ions can activate transcription factors, such as CREB, which bind to specific DNA sequences and promote or inhibit the transcription of target genes. Calcium-dependent kinases can also phosphorylate transcription factors, enhancing their activity.</p> Signup and view all the answers

Describe how the distribution of ions can be used to determine the positivity or negativity of a cell.

<p>The relative concentration of positive and negative ions inside and outside the cell determines its charge. A cell with more positive ions outside is positively charged, while more positive ions inside results in a negative cell.</p> Signup and view all the answers

Explain the molecular mechanism by which an extracellular ligand binding the receptor and initiating a cellular response. What types of receptors are used?

<p>Extracellular ligand binding to a receptor initiates a cascade of intracellular events, altering cell function. Receptor activation triggers signaling pathways that amplify the signal. Types of receptors include ion channels and transmembrane receptors.</p> Signup and view all the answers

What would occur to the body during the flight or fight response if one were to block the action of adrenaline? What are the specific targets that would be affected?

<p>Blocking adrenaline would impair the body's ability to respond to stress. This impairment would affect heart rate, metabolism, and the release of glucose, thereby reducing the energy available for fight or flight.</p> Signup and view all the answers

Flashcards

Signaling

The cascade of processes by which an extracellular stimulus affects a change in cell function.

Signaling through ion channels

Proteins embedded in the membrane that open to allow ions to flow across.

Signaling through receptors

When a signal binds to a receptor protein, initiating a series of events that change cell function.

Selective ion channels

Ion channels often allow only specific ions to pass through.

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Calcium (Ca2+) in signaling

A ubiquitous signaling ion involved in exocytosis, contraction, metabolism, and more.

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Exocytosis

The process where cells release substances to the outside through vesicles.

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Contraction

The ability of muscle cells to shorten and generate force.

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Metabolism

All chemical processes involved in maintaining life.

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Gene Transcription

The process of creating new DNA and RNA from a DNA template.

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Fertilization

The fusion of sperm and egg to produce a zygote.

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Proliferation

An increase in cell number, leading to tissue growth.

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Hypertrophy

Increase in the size of cells or organs, leading to increased tissue mass.

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Membrane potential

The slight electrical imbalance across a cell membrane.

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Electrochemical gradient

The sum of electrical and chemical forces acting on an ion.

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Passive ion transport

Transport of ions across a membrane down their electrochemical gradient.

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Active ion transport

Transport of ions across a membrane against their electrochemical gradient.

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Ion gradients

Generated by active transport; requires ATP to move ions against their concentration gradient.

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Na+/K+ pump

An enzyme that hydrolyzes ATP to maintain gradients of Na+ and K+ across the plasma membrane.

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Calcium pump

An enzyme that uses ATP to create calcium gradients across the plasma membrane.

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Uniport

Transports one type of molecule in one direction.

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Symport

Transports two or more different molecules in the same direction.

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Antiport

Transports two or more different molecules in opposite directions.

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Sodium-calcium exchanger (NCX)

Uses the sodium gradient to move calcium out of the cell

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Study Notes

  • Signalling involves a cascade of processes initiated by an extracellular stimulus, like a neurotransmitter or hormone, to change cell function.

Examples of Signalling

  • Glutamate acts as a neurotransmitter for nerve-to-nerve transmission (neurotransmission).
  • Adrenaline triggers a flight or fight response.

Types of Signalling

  • Signalling through ion channels occurs when proteins embedded in the membrane open, allowing ions to flow through.
  • Signalling through receptors involves a signal binding to a receptor protein, initiating a cascade of events that changes cell function.

Signalling Through Ion Channels

  • Ion channels are often selective for particular ions, allowing movement of different ions.
  • For example, Potassium channels only allow Potassium to enter the cell, and Calcium and Sodium channels work similarly.
  • Calcium is a ubiquitous signalling ion that is used throughout signalling in many ways
  • For example, calcium levels spike during egg fertilization with sperm

Calcium Signalling

  • Involved in exocytosis, contraction, metabolism, gene transcription, fertilization, proliferation, and hypertrophy.
  • Cell membranes are normally impermeable to ions.
  • Gases freely travel across membranes.
  • Ions like sodium, potassium, calcium, and chloride, being charged, are usually prevented from crossing the membrane.
  • Channel proteins transport ions across membranes.
  • Differences in ion concentrations across membranes are significant

Ion Transport

  • Can be either passive or active.
  • Passive transport includes simple diffusion, channel-mediated, and carrier-mediated mechanisms.
  • Active transport requires energy.
  • Passive transport is determined by the electrochemical gradient.
  • Cells have a membrane potential, resulting in a slight electrical imbalance.
  • The inside of the cell is negative relative to the outside, which has a lot of positive charge resulting in flow from outside to inside.
  • Both electrical and chemical gradients affect ion transport such that positive goes to negative.

Ion Concentrations (mM)

  • Intracellular: Na+ (5-15), K+ (140), Mg2+ (0.5), Ca2+ (10^-4), H+ (7 x 10^-5 or pH 7.2)
  • Extracellular: Na+ (145), K+ (5), Mg2+ (1-2), Ca2+ (1-2), H+ (4 x 10^-5 or pH 7.4), Cl- (110)

How Ion Gradients Are Generated

  • Generated by active transport
  • Energy is required to move ions against their concentration gradient.
  • This process requires ATP to drive uphill movement of ions.

Sodium - Potassium Pump

  • Generates sodium and potassium gradients across the plasma membrane.
  • For every molecule of ATP hydrolysed, 3 sodium ions are moved out and 2 potassium ions are moved in.
  • This is an active transport process where ATP is hydrolysed to ADP + Pi.
  • Sodium is ejected out of the cell, and potassium is transported into the cell.
  • This pump is a P-type ATPase
  • "P" stands for phosphorylation as sodium can bind easily to the protein causing its phosphorylation by ATP, driving a conformational change that releases sodium.

Calcium Pump

  • Generates calcium gradients across the plasma membrane.
  • PMCA (Plasma Membrane Calcium ATPase) keeps calcium concentration low inside the cell by ejecting calcium outside using a P-type ATPase.
  • SERCA (Sarco/endoplasmic reticulum Ca2+-ATPase) also uses a P-type ATPase to generate calcium gradients across intracellular stores.
  • It takes calcium from the cytoplasm to the lumen of the ER or SR.

Ion Gradients Used For Secondary Transport

  • Involve uniport, symport (coupled in the same direction), or antiport (coupled, opposite directions).
  • Sodium gradient is used to drive Calcium efflux via the Sodium/Calcium exchanger (antiporter).
  • NCX exchanges 2 Sodium in for Calcium out.

Ion Channels

  • Voltage-gated and have 6 transmembrane regions (S1-S6).
  • They have 2 domains
  • The first 4 building blocks form a voltage-sensing domain that responds to voltage to open the channel.
  • The last 2 building blocks (S5, S6) form the pore domain, which has a hole through which ions flow.
  • Voltage-gated K+ channels have 4 subunits.
  • Sodium/Calcium channels have 4 linked subunits.

Gated Channels

  • Can be ligand-gated (extracellular or intracellular) or mechanically gated.

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