Control of Potassium

We need to regulate potassium as it determines the resting membrane potential.

– As the relative permeabilities of sodium and calcium are very low, K+ is the main determinant.

– Normal extracellular [K+] = 4mM

– Intracellular [K+] = 125mM

– As the extracellular space much smaller than intracellular 16:24 litres, changes in [K+] extracellular affect Em greatly.

Why K+ changes

The Potassium concentration can change for many reasons:

– Changes in intake –> average of 100mM K+ eaten per day, but starvation may decrease this

– Inability to absorb it –> inflammation of the bowel

– Excessive loss –>  this can occur in vomiting/diarrhea


The K+ may also change in the body due to intracellular-extracellular shifts:


– Dehydration –> increase in plasma osmolality causes cell shrinkage, so cells lose K+ in response

– Acidosis –> in acidosis, protons move into the cell where they are buffered by proteins, so K+ ions move outwards to compensate.


– Hyperhydration

– Adrenaline –> this activates the Na/K-ATPase, which shifts potassium into cells

– Insulin –> activates the Na/K-ATPase and increases Na+ entry via the Na-glucose transporter.

Regulation of Potassium

The [potassium] can be regulated by controlling both internal balance and the external balance.



There are specific feedforward responses to eating and exercise:

– When eating, insulin stimulates the Na/K-ATPase to drive potassium into cells.

– Adrenaline increases activity of the pump shifting K+ into cells, to stop becoming hyperkalaemic in exercise.



– Long term K+ homeostasis requires the kidneys.

– However, potassium is freely filtered by the kidneys and reabsorption is unregulated

– Regulation of potassium is controlled by the principal cells in the late DCT which control secretion.


The sodium pump in basal membrane creates a sodium gradient

– Sodium then diffuses into the cell via ENaC channels from the lumen in order to balance the gradient.

– To balance the charge, potassium diffuses out via ROMK channels, and so it is excreted in the urine

Control of K+ secretion is increased in 3 main ways:

i) High plasma [K+] – enhances transport into principal cells

ii) Aldosterone – stimulates synthesis of ROMK + ENaC channels and sodium pump density, increasing secretion

iii) High tubular flow rate – removes K+ in tubule allowing more secretion.

Consequences of High and Low potassium


This hyperpolarizes the cell and reduces the excitability of nerve and muscle

– Leads to muscular weakness –> muscular paralysis + cardiac arrhythmias + lethargy.

– T waves disappear as cells repolarize slower and are replaced by U waves


This is often due to renal failure where GFR drops below 20% to prevent excretion.

– Depolarizes cells bringing them closer to threshold, giving hyperexcitability

– Leads to cramps, spasms, diarrhea and increasing chances of cardiac arrhythmias (ventricular fibrillation)

– T wave gets larger as cells repolarize faster.