Human Physiology 2

Why is too much K+ toxic?

May cause nausea, vomiting, diarrhea, and/or ulcers

What change in membrane potential does hyperkalemia causes

depolarize the membrane bringing it closer to its threshold, now stimulus that would normally be subthreshold can cause an action potential

What change in membrane potential does hypokalemia cause

hyperpolarizes the membrane, making it less likely to fire an action potential that would normally cause one

What are the passive fluxes to maintain the resting potential?

sodium and potassium move across the membrane by leak channels

What are the active fluxes to maintain the resting potential?

ATP/energy moves sodium and potassium across the membrane

The stages of action potential

resting potential, depolarization, repolarization, hyperpolarizatio

Resting potential permeability

All Na and K gates are closed

Depolarization membrane permeability

Na

Hyperpolarization membrane permeability

H

What are the two types of refractory periods?

Absolute and relative

Absolute refractory period

All voltage-gated Na+ channels are inactivated. No action potential can be induced.

Relative refractory period

Some voltage-gated Na+ channel have transitioned from inactivated state to closed state, but K+ channels remain open. The membrane will require a greater stimulus to cause an action potential of a smaller size

What is graded potential? How does it differ from action potential?

Changes in membrane potential that are confined to a relatively small region of the plasma membrane. Action potential is not confined to a small area

What determines the threshold of an action potential?

a graded potential which can induce positive feedback to open more and all of the voltage-gated Na+ channels

What is an excitable cell?

electronically excite cell resulting in the generation of action potentials

Which type of ion channel is necessary for excitable cells?

Neurons, muscle cells, and some endocrine cells

The two different communication systems in the body

local and long-distance

Difference between local and long-distance communication

local communication occurs within a small, defined area, while long-distance communication spans greater distances, more energy and higher costs.

What are the ways of local communication between cells?

Gap junctions, contact-dependent, autocrine, and paracrine signals

Steps in signal transduction

The chemical signal is a ligand that
binds to the receptor and is the first
messenger.
Ligand-receptor binding activates the
receptor.
The receptor activates one or more
intracellular signal molecules.
The last signal molecule modifies
existing proteins or initiates the
synthesis of new proteins.

Antagonist

A molecule that competes with a
ligand for receptor, but does NOT activate
signaling.

Agonist

A molecule that mimics a ligand to bind
to the receptor, and activates signaling

Kd is

The dissociation constant, is commonly used to describe the affinity between a ligand and a protein. Kd is equal to the concentration of ligand at which half of the
proteins are occupied.

Higher Kd means

Lower affinity

Liver cells, skeletal muscle blood vessels, and intestinal blood vessels are all under the
control of epinephrine, why do they show different effects with epinephrine present?

They either have a different receptors or intracellular proteins

Liver cells and the effect of epinephrine

Beta receptor: glycogen breaks down and glucose is released from the cell

Skeletal muscle in blood vessels and the effect of epinephrine

Beta receptor: The blood vessel dilates

Intestinal blood vessel

Alpha receptor: blood vessel constricts

What is the benefit of the cascade signal transduction

Cascade signal transduction allows multiple point of regulation and signal amplification.

What are the differences between intracellular receptors and cell-surface receptors

Cell surface receptors are hydrophilic and intracellular receptors are hydrophobic

What are the four types of surface receptors?

Receptor channel, g protein-coupled receptor, receptor-enzyme, and integrin receptor

How does a steroid molecule affect the target cell?

The estrogen-receptor complex binds to DNA and regulates gene activity

What signaling pathway that NO activates to dilate blood vessels

Nitroglycerin

What is integrin?

Cell surface receptors that are composed of two subunits, α and β, and each αβ combination has its own binding specificity and signaling properties.

Most integrins recognize extracellular-matrix (ECM) proteins.
As integrins bind to ECM, they become clustered in the plane of the cell
membrane, which promotes the assembly of actin filaments

What is its role in leukocyte extravasation?

Integrin binding slows down white blood cells (WBC) and initiate actin
cytoskeletal remodeling

What is the mechanism of receptor tyrosine kinase?

1. Signal molecules bind to the receptor monomer
2. Two monomers combine to make dimers.
3. Dimerization activates phosphorylation of tyrosines in a receptor’
4. The phosphorylated receptor becomes a kinase and can phosphorylate other intracellular proteins.

How does receptor tyrosine kinase relate to cancer?

RTKs are often aberrantly activated through mutations, gene amplification, or fusion proteins, leading to uncontrolled cell growth

What are the four types of breast cancer based on receptor types

Luminal A, Luminal B, HER2-positive, and Triple-negative

Structural features of GPCR and G protein

Seven trans membrane regions and alpha, beta, gamma, subunits

Describe the signal transduction mechanism of GPCR

• Ligand binds to the inactive receptor is a protein complex.
• The binding of a ligand to the receptor changes the
conformation of the receptor.
• This activated receptor increases the affinity of the alpha subunit of the G protein for GTP.
• When bound to GTP, the alpha subunit dissociates from the beta and gamma subunits.
• This dissociation allows the activated alpha subunit to link up with still another plasma membrane protein, either an ion channel or an enzyme.

What are the two types of acetylcholine receptors?

Nicotine and Muscarine

Nicotinic mechanism

Type: ligand-gate ion channel

Ion flow: Na+ and K+

Effect on Vm: Depolarization

Excitability: Increase

Location: Skeletal muscle

Muscarinic mechanism

Type: GPCR

Ion flow: K+

Effect on Vm: Hyperpolarization

Excitability: Decrease

Location: Heart

cAMP pathway

• G alpha-GTP activates adenylyl cyclase (AC).
• Active AC converts ATP to cAMP.
• cAMP activates PKA
• PKA may affect gene expression (e.g.
related to learning and memory)

What is the cellular effect of caffeine that is related to cAMP?

Caffeine inhibits PDE therefore promotes the accumulation of cAMP

Where is Ca2+ stored in the cell?

Extracellular fluid and ER

What is calmodulin?

A calcium-binding messenger protein

Which enzyme produces, degrades, and is the target of cAMP in a cell?

Generate: AC

Degrade: PDE

Active: Protein kinase A

Homeostasis and example

Regulation of the internal environment. Body temperature

Alpha cells in the pancreas

glucagon —→ increases glucose in blood

Beta cells in the pancreas

insulin ——> decreases glucose in blood

Negative feedback

The response counteracts the stimulus, shutting off the response loop

Positive feedback

The response reinforces the stimulus, sending the variable farther from its setpoint

Feedforward system

regulation anticipates changes in a regulated variable, improves the speed of the body’s homeostatic responses.

An example of Negative feedback

Insulin

An example of Positive feedback

Pepsinogen and pepsin in the stomach

An example of feedforward system

Heart rate increases before a race

Acclimatization

the process by which an individual organism makes changes in response to its environment

How are biological rhythms related to homeostasis? Are they feedback or feedforward?

Biological rhythms enable homeostatic mechanisms to be utilized immediately and automatically by activating them at times when a challenge is likely to occur but before it actually does occur. Feedforward.

Plasma cortisol is lowest during

Plasma cortisol is highest

sleep

awakening

Body temperature is lowest

Body temperature is highest

morning and night

Circadian rhythm

What is reflex?

Any response that occurs automatically without conscious effort.

Describe the Biceps stretch reflex

assesses the integrity of the C5 and C6 spinal nerve roots by tapping the biceps tendon, which causes the biceps muscle to contract and the forearm to flex.

What are the two types of reflexes?

Simple reflex is an unlearned and predictable responses. Acquired reflex is a result of practice and learning.

Insulin release reflex

When blood glucose levels increase after a meal, this triggers receptors that signal the pancreas to release insulin

Ferguson reflex

The pushing of the baby against the cervix causes the cervix stretch which stimulates the release of oxytocin, which the causes uterine contractions and then the process repeats

Salivation reflex

Seeing, smelling, or even thinking about food can trigger this

Shivering reflex

When the body's temperature drops, the brain detects the cold and initiates shivering, which are involuntary, rhythmic muscle contractions that generate heat to warm the body

What is circadian rhythm?

The body's natural, 24-hour internal clock, regulates physical, mental, and behavioral changes in response to light and dark.

How does the circadian rhythm differ from the human endogenous rhythm? Which
environmental cue affects the circadian rhythm?

The human endogenous rhythm is an 25 hour clock and doesn’t respond to stimulus like light