Session 2: Membranes, solutes, diffusion, and transport

cell membranes are primarly composed of

lipids and proteins

lipids can include

phospholipids

cholesterol

glycolipids

proteins can include

transporters

enzy,es

hormone receptors

cell surface antigens

ion + water channels

Cell membranes are responsible for the high permeability of the membrane to lipid soluble substances such as

carbon dioxide, oxygen fatty acids, and steroid hormones 

cell membranes are also barriers for pathogens and xenobiotics, which are

chemical compounds foreign to a living organism (drugs, pesticide, carcinogen)

integral membrane proteins

embedded or anchored to cell membrane

peripheral membrane proteins

not embedded in the membrane, loosely attached to either IC of EC side of the membrane by ionic interactions

what are two examples of why membrane transport is critical for medicine

1. neuromuscular junctions and control of muscle activity

2. membranes control the activity of pharmaceutical agents

total body water is distributed between

ICF (2/3) and ECF (1/3)

Plasma is part of the ___, and is the fluid

ECF, circulating in blood vessels

what is the major cation of ECF

sodium (Na+)

what are the balancing anions of ECF

Cl- and bicarbonate (HCO3-)

what is the major cations of ICF

potassium (K+) and Magnesium (Mg 2+)

what are the balancing anions of ICF

proteins and organic phosphates

What maintains the different composions of ICF and ECF

energy consuming transport mechanisms, or transporters, in the cell membrane

simple diffusion occurs due to random _______ (______) motion of molecules

thermal (brownian)

in simple (passive) diffusion of solutes, there is a ______ _______ of two solutions that will continue until the solute concentrations of both solutions becomes equal

net diffusion

in clinical practice, hemodialysis is used as a treatment for

kidney failure to filter solute waste from the blood

in hemodialysis, blood passes through a tube line with an ______ _______ that is permeable to solutes in the blood

artificial membrane

in hemodialysis, the solutes pass through the membrane, down the conc. gradient) to the other side, which

lowers the conc of waste solutes in the blood

The chemical nature of a solute impacts its diffusion across a phospholipid membrane based on

• ionization (charged molecules diffuse at at slower rate)

• molecular size (large molecules slow)

• partition coefficient (K) (lipid soluble diffuse faster than water soluble)

partition coefficient

describes the solubility of a solute in oil relative to its solubility in water

nonpolar solutes tend to be soluble in oil and have a

K>1

polar solutes tend to be insoluble in oil and have a

K<1

K can be measured by

adding the solute to a mixture of oil and water and then measuring the conc in each phase

drug design is largely driven by

ionization and solubility of the compound

drugs are often designed as mixtures of

charged and uncharges states

what types of forms can penetrate the cell membrane more in drugs

lipid soluble and uncharged

the diffusion rate of a drug is based on the equilibrium between its

water solubility and membrane permeability

What are the two types of protein membrane carriers

ion channels and transporters

ion channels

Allow ions to flow through the membrane down a concentration gradient.

Tranporters

Consists of a channel that opens to receive a solute, the solute is passed
through the transporter and released on the other side of the membrane.

Facilitated diffusion is driven by a conc. gradient. it is not dependent on

cellular energy (ATP)

channels and transporters enable the rapid transit of

large and/or charged molecules

facilited diffusion is faster, but it is limited by the

number of transporter proteins

simple diffusion is slower, but it cannot be

saturated (think the grocery lane example)

transporters display substrate

stereospecificity

at low concentrations, which diffusion is better

facilitated

as high concerntrations, which diffusion is better

simple

transporters can recognize chemically similar solutes. what is an example of this

GLUT4 tran

Ca2+ ATPase is present in

sarcoplasmic reticulum and endoplasmic reticulum

H+-K+ ATPase is present in

gastric and renal cells

for active transport, energy in the form of _ ____ must be provided

ATP hydrolysis

primary active transport

when ATP hydrolysis is directly coupled to the transport process

For Na+-K+ ATPase, the transporter changes its conformation when it is ________, which changes the affinity for Na+ and K+

phosphorylated (addition of phosphate group)

For the Na+ -K+ ATPase, each ion moves against its own electrochemical gradient. The stoichiometry can vary, but, in general, for every ___ Na+ ions pumped out of the cell, ___ K+ ions are pumped into the cell

3 Na+ out of cell

2 K+ into the cell

Na+ -K+ ATPase is termed electrogenic because it creates

a charge separation and a potential difference across the membrane.

For each cycle of the Na+ -K+ ATPase, more ________ _____ (Na+) is pumped out of the cell than is pumped into (K+) the cell.

positive charge

what class of drugs inhibit Na+ -K+ ATPase

cardiac glycosides (digitalis)

Collies and other herding breeds (Old english sheepdog, shetland sheepdogs) are more likely to have a deletion mutation in their

MDR1 (multi-drug-resistant 1 or P-glycoprotein)

P glycoprotien moves ________ out of the cell and away from the brain in the bloodstream

xenobiotics

MDR1 mutation causes a functional P-glycoprotein defect, which limits the

activity of the ATP transporter

ivermectin

substrate of P glycoprotein

antiparasitic drug used to treat heartworms and other parasites

If you give an MDR1 mutation dog ivermectin, what occurs

slows drug effluc and causes accuulation of ivomec - causes seizures and toxicosis

dogs with sensitivity to ivermectin can show symptoms of toxicity within 

4-6 hours of exposure

what are signs of toxicosis (not on exam)

a. Neurologic signs: shaking, disorientation, stumbling, seizures, and even coma.
b. Pupil Dilation: A common early sign is the dilation of the pupils and increased sensitivity to
light.
c. Appetite and Digestive Problems: Affected dogs may experience inappetence, vomiting,
and/or diarrhea.
d. Motor Impairment: As the symptoms progress, dogs can fall or stagger as they stand or walk.
They can also seem disoriented.
e. Lethargy: Lack of energy is another early indication of toxicity.