lec 8 - solute transport

membrane transport overview

transport of solutes can be classified by the type of energy used or the solutes pathway across the plasma membrane

pasisve transport moves solutes down a gradient - potential energy from concentration or electrochemical gradients

active transport moves solutes up a gradient - using ATP either directly or indirectly

lipophobic molecules (e.g. ions) require transmembrane proteins to cross the phospholipid bilayer 

diffusion

spontaneous movement of individual molecules from a region of hgih cncentration to a region of low concentration

flux

describes the magnitude and direction of solute movement

defined as the diffusion rate per unit surface area of the membrane

proportional to concentration gradient x permeability coefficient

fluxes at equilibrium

unidirectional fluxes still occur but they are equal and opposite so cancel out and net flux at equilibrium is 0

flux equation 

Jx = Px ([X]i-[X]0)

linear relationship - increase in concentration gradient = increase in flux

membrane permeability coefficient

represents how easily a solute crosses a membrane

Px is proportional to lipid solubility/molecular size

aquaporins

non-gated tunnel, which allow water molecules to move down as osmotic gradient 

highly selective for water over ions 

selectivity filter formed by conserved asparagine residues which prevents ion passage 

arrange water molecules one by one through a narrow pore 

ion channels

electrochemical gradient dependant

channels can. be open to ECF and ICF at the same time

ion channels are not continuously open (gated) - open wither spontaneously or in response to specific stimulus

specificity is variable and based on channel type

can be regulated by changing open probability pr the numbver of channels in the membrane

open probability

how long a channel is open for

types of important ion channels in epithelial physiology

ENaCs - sodium channels found in tight absorptive epithelium

CFTR - apical membrane channel that transports both Cl- and HCO3- 

carriers (uniporters)

facilitated diffusion - transports solutes (e.g. sugars, amino acids) down a concentration gradient 

binding of the solute triggers a conformational change in the carrier protein 

carriers never forma. continuous connection between the intracellular and extracellular fluid 

symporters (cotransporters)

secondary active transport - indirectly use energy by moving one solute (eg Na+) down its electrochemical gradient to move another solute up its electrocheical gradient

moves two or more solutes in the same direction

exchangers (antiporters)

indirectly use energy by moving one solute down its electrochrmical gradient to move another solute in the opposite direction

generally exchange cations for cations or anions for anions 

essential for acid base balanc and pH refulation 

primary active transporters (pumps)

use ATP hydrolysis to move ions against electrochrical gradient - undergoes a series of conformational changes 

in epithelia the Na+/K+ATPase is essential for vectorial transport 

maintains electrohrmical gradents to drive transport 

inhibiting transporters and channels

ion channels and transporters can be blocked or inhibited by different pharmacological compounds

used in the lab to study a specific channel or transporter

also used to clinically treat different conditions - e.g. type II diabetes (SGLT2 inhibitors) or hypertension (thiazides inhibit Na+/Cl- symporters) 

transporter saturation

transporters undergo binding, conformational change and release cycle, making them vulnerable to saturation

transport flux increases with solute concentration until it reaces a maximum rate (Jmax) when all carriers/transporters are occupied 

solute competition

transporters have veraible affinities for different solutes

a transporter may move several structurally similar solutes, but those solutes compete with one another for transporter binding sites