Na-K Pump

[NPO]

By what action does insulin stimulate the Na-K pump? The context is giving glucose and insulin for hyperkalemia.

 

[Brandon O]

If you mean the actual cellular mechanism, I'm not sure. Here's a bit of discussion.

If you mean wherefore it happens, the explanation I've heard is to help sequester post-prandial potassium. You chow down on some K, it hits your bloodstream, then the insulin release helps tuck it away intracellularly to limit the effect on serum potassium until you can gradually clear it.

 

[Brandon O]

There's a similar story in why epinephrine stimulates the Na/K pumps. Exercise causes skeletal muscle to leak potassium (quite a lot of it), but the associated adrenergic response drives it back in within a few minutes of rest. Thus albuterol.

 

[systemet]

I'd always assumed that because glucose enters cells via Na+ symport, that because the [Na+]intracellular goes up, the Na+/K+-ATPase is stimulated, causing expulsion of sodium, and intracellular accumulation of potassium.

I guess another likely possibility, is that that after glucose enters the cell, more ATP is produced, inhibiting ATP-dependent KATP channels, causing less K+ efflux.

 

[systemet]

Ok. Pulled the paper, a few relevant pieces:

"the intracellular concentration of Na+([Na+]i) under prevailing basal conditions is not saturating, therefore increases in [Na+]i alone suffice to increase pump activity by mass action"

"stimulation elicited by hormones is only approximately 5% of the increase in Na+/K+-ATPase activity caused by maximal electrical stimulation of muscle"

* The paper suggests that insulin also causes a change in the subunit contribution of Na+/K+-ATPase in muscle cell membranes, increasing the activity.

* In addition to sodium symport, insulin may increase Na+ influx by stimulating Na+/H+-antiporters and Na+-K+/2Cl- transporters (which also increases intracellular K+), and further stimulates Na+-K+-ATPase.

* Phosphorylation events on the Na+/K+-ATPase, which increase activity, via various potential kinase pathways, e.g. PKC, PI3K, MAPK [I wonder if there might also be a loss of an inhibitory phosphorylation event via AMPK.]

* Long-term increases in expression of the transporter.

So essentially you're looking at (1) an increase in Na+/K+-ATPase activity simply because intracellular Na+ has increased (as a consequence of Na+-glucose symport, NHE or Na+K+2Cl- activation), (2) a shift towards more highly active subunits in response to insulin, (3) an increase in the number of transporters at the membrane, and (4) an increase in the activity of the transporters via phoshoregulation.

This is a little bit of an older review paper, so on one hand, most of it is probably true. On the other hand, there undoubtedly additional nuances that have been described, some of them probably speculative.

 

[systemet]

I'd always assumed that because glucose enters cells via Na+ symport,.

Just wanted to added, that this statement I made earlier is a little misleading. Glucose enters intestinal cells via Na+ symport, e.g. SGLT transporters. This prevents glucose from being drawn out of the intestinal epithelia between meals, when intestinal [glucose] may be low, and allows uptake when [glucose] in the intestines is < [glucose] in the gut epithelium. So this is likely a minor mechanism.

The majority of cell types use facilitated diffusion for glucose uptake, via GluT channels. In terms of insulin's action, you're primarily looking at increased GluT4 expression in muscle and adipocytes. Most of the other GluT family members are insulin-insensitive.

 

[systemet]

There's a bit of a discussion on glucose transport here (mostly related to the CNS).

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134675/

 

[Brandon O]

Just wanted to added, that this statement I made earlier is a little misleading. Glucose enters intestinal cells via Na+ symport, e.g. SGLT transporters. This prevents glucose from being drawn out of the intestinal epithelia between meals, when intestinal [glucose] may be low, and allows uptake when [glucose] in the intestines is < [glucose] in the gut epithelium. So this is likely a minor mechanism.

Was curious about that. I've mainly heard of sodium/glucose cotransport only in the intestines and kidneys.

 

[systemet]

Was curious about that. I've mainly heard of sodium/glucose cotransport only in the intestines and kidneys.

Yeah, you're right - I should have fact-checked before I posted, but I was going for memory and got a few things confused.

Re: active transport, I think you need it primarily where you're going to potentially be transporting up a gradient, or you have a risk that the gradient may reverse for periods of time, and you need to have unidirectionality of transport.

 

[Bobbob1354]

I'd always assumed that because glucose enters cells via Na+ symport, that because the [Na+]intracellular goes up, the Na+/K+-ATPase is stimulated, causing expulsion of sodium, and intracellular accumulation of potassium.

I guess another likely possibility, is that that after glucose enters the cell, more ATP is produced, inhibiting ATP-dependent KATP channels, causing less K+ efflux.

When a cell depolarizes it is a massive influx of Na+ into the intracellular space, during repolarization K+ actual leaves the cell to bring the resting membrane potential back to its normal voltage. Sodium potassium pumps just help maintain the electrochemical gradient that is necessary for cells to live and communicate