lec 11 - cellular models of transport

tight epithelia and Na+ homeostasis

the final checkpoint for Na+ balance and blood pressure regulation

tight epithelia of the distal nephron reabsorb a relatively small but critical fraction of filtered Na+

even a few % change here can shift ECF volume and therefore blood pressure

hormonal control (aldosterone or ANP) enables precise control

leaky absorptive epithelia

transport from the mucosal to serosal solution

epithelial ells in the small intestine and proximal tubule absorb large quantities of Na+, glucose, amino acids and several other solutes 

these tissues prioritise speed and bulk transport over precise regulation 

secondary active transporters drive the absorption of solutes from the luman across the apical membrane 

secretory epithelium

leaky allow paracellular water transport (isotonic secretion)

generally secretion of isotonic NaCl in the lumen is driven by Cl- secretion primarily through apical CFTR channes

required in many tissues: exocrine glands of the GI tract, respiratory epithelium, reproductive tract

electrogenic Cl- secretion

regulation of Cl- secretion why/how

to maintain the electrochemical driving force for Cl- movement

if Vm = ECl (-34.7mV) there is no net transport and secretion stops 

Cl- secretion increases GCl during Cl- secretion which pulls Vm towards ECl 

prevent this by increasing GK (open or insert more basolateral K+ channels) 

K+ efflux keeps Vm below ECl 

regulation of Cl- secretion - inputs 

hormonal and neural inputs modulate intracellular cAMP or intracellular Ca2+ to control Cl- secretion 

cAMP → activates PKA → phosphorylates CFTR → increases channel open probability 

concurrently increases the actvity of PKA/cAMP activated basolateral K+ channels

Ca2+ increases open probability of Ca2+ sensitive basolateral K+ channels