Less Extracellular Ca2+ == Increased Neural Excitability

[justadream]

TBR Bio I page 308 #53

"Hypoparathyroidism is BEST characterized by"

Answer: Increased neural excitability

Answer Explanation: "A decrease in calcium in the extracellular fluid allows more sodium to flow through the membranes of nerve cells"

Can someone explain this? Is is because with less calcium, the resting membrane potential becomes more positive (and easily depolarized)?

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[Marleywh]

I don't think the specifics are important but I think I remember from a physio class that Ca2+ has as inhibitory effect on Na-channels.

 

[justadream]

Bump.

 

[kraskadva]

Can you post the whole question and answer choices?

 

[justadream]

Incorrect choices:

Increased osteoblast activity
Increased osteoclast activity
Increased plasma Calcium concentrations

 

[kraskadva]

Nothing else in the question stem?

 

[justadream]

Nothing else in the question stem?

Nope.

 

[Cawolf]

I can't really elaborate, but I have come across basic information that agrees with your initial statement.

The calcium cations alter the resting potential, which results in easier depolarization.

 

[justadream]

@Cawolf

Would you agree that:

Increased extracellular Ca2+ leads decreased neural excitability but INCREASED muscle excitability?

Since having more Ca2+ allows more Ca2+ to cause muscle to contract?

 

[Cawolf]

So now we are talking about hypercalcemia, correct?

I would imagine it would have the effect of decreasing nervous excitability - but I have never read anything along those lines in the literature.

Muscle excitability. . . that is actually associated with hypocalcemia as well - look up tetany. It has the same mechanism as with the neural excitability.

You do see the effect of hypercalcemia in cardiac muscle though. It is common for ECG abnormalities to present with such a patient.

 

[justadream]

There is actually an AAMC question on this topic that talks about a different mechanism (I think?).

Anyone can PM me for details.

 

[kraskadva]

TBR Bio I page 308 #53

"Hypoparathyroidism is BEST characterized by"

Answer: Increased neural excitability

Answer Explanation: "A decrease in calcium in the extracellular fluid allows more sodium to flow through the membranes of nerve cells"

Can someone explain this? Is is because with less calcium, the resting membrane potential becomes more positive (and easily depolarized)?

Incorrect choices:

Increased osteoblast activity
Increased osteoclast activity
Increased plasma Calcium concentrations

Ok, I find this question weird on a couple of levels, but first with the answer...

The parathyroid makes parathyroid hormone which increases Ca2+ in the blood. If you have hypoparathyroidism, then you would have less parathyroid hormone and so less Ca2+ in the blood.
This automatically eliminates the last answer (Increased plasma Calcium concentrations)
PTH also upregulates osteoblasts and (I think) downregulates osteoclasts. So a lack of it would eliminate (Increased osteoblast activity) and make (Increased osteoclast activity) a potential answer.
Ca2+ moving into the cells make neurons release neurotransmitters and make muscle cells contract. Lack of Ca2+ would on the face of it seem to have the opposite effect. But with the explanation TBR is giving (A decrease in calcium in the extracellular fluid allows more sodium to flow through the membranes of nerve cells) I'm not really sure what to think. To my mind, I would think a decrease in Ca would decrease the electrical gradient across the membrane (by having fewer cations in the ECF) and make the Na+ less likely to cross the membrane, since there would be less of a negative charge to pull it in. And so, less neural excitability. But I may not be reasoning through the membrane potentials correctly. Here and here are couple of other threads talking about this.

IDK, it just seems weird to me. The AAMC says you should know major hormones (and I think PTH would probably qualify), and that you should know about membrane potentials and the action of Ca2+ on muscles, but for nerves they only specify Na+/K+ for action potentials. Also, I can't remember seeing such a bare bones question stem for this level of a question in any AAMC or MCAT material.

 

[sillyjoe]

TBR Bio I page 308 #53

"Hypoparathyroidism is BEST characterized by"

Answer: Increased neural excitability

Answer Explanation: "A decrease in calcium in the extracellular fluid allows more sodium to flow through the membranes of nerve cells"

Can someone explain this? Is is because with less calcium, the resting membrane potential becomes more positive (and easily depolarized)?

Under normal conditions a few calcium ions flow through the sodium channel even though it is mostly sodium ions flowing through. When you are hypocalcaemic those calcium ions do not flow through the sodium channel and thus allow for more sodium ions to flow through.

In addition, as mentioned above, calcium has an inhibitory effect on the sodium channels. A decrease in extracellular calcium causes a disinhibition of the sodium channel and consequently an increase in neural excitability.

 

[justadream]

@kraskadva

"PTH also upregulates osteoblasts and (I think) downregulates osteoclasts."

Isn't this backwards?

I thought that the goal of PTH is to INCREASE blood Ca2+ levels. This would occur by increasing bone breakdown (upregulating osteoclasts) while inhibiting bone formation (downregulating osteoblasts).

 

[kraskadva]

@kraskadva

"PTH also upregulates osteoblasts and (I think) downregulates osteoclasts."

Isn't this backwards?

I thought that the goal of PTH is to INCREASE blood Ca2+ levels. This would occur by increasing bone breakdown (upregulating osteoclasts) while inhibiting bone formation (downregulating osteoblasts).

Perhaps... I'm looking again, but not finding a definitive answer.

http://en.wikipedia.org/wiki/Parathyroid_hormone
I initially read this:

In osteoporotic women, administration of an exogenous parathyroid hormone analogue (teriparatide, by daily injection) superimposed on estrogen therapy produced increases in bone mass and reduced vertebral and nonvertebral fractures by 45 to 65%.

and thought that it would increase bone.
But reading through more carefully, I saw this:

It enhances the release of calcium from the large reservoir contained in the bones.[7]Bone resorption is the normal destruction of bone by osteoclasts, which are indirectly stimulated by PTH. Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather, PTH binds to osteoblasts, the cells responsible for creating bone. Binding stimulates osteoblasts to increase their expression of RANKL and inhibits their expression of Osteoprotegerin (OPG). OPG binds to RANKL and blocks it from interacting with RANK, a receptor for RANKL. The binding of RANKL to RANK (facilitated by the decreased amount of OPG available for binding the excess RANKL) stimulates these osteoclast precursors to fuse, forming new osteoclasts, which ultimately enhances bone resorption.

So I'm just confused now too.

 

[sillyjoe]

@kraskadva

"PTH also upregulates osteoblasts and (I think) downregulates osteoclasts."

Isn't this backwards?

I thought that the goal of PTH is to INCREASE blood Ca2+ levels. This would occur by increasing bone breakdown (upregulating osteoclasts) while inhibiting bone formation (downregulating osteoblasts).

PTH indirectly activates osteoclastic activity (bone resorption) through a mechanism where PTH causes an inhibition of a paracrine factor in osteoblasts that inhibits osteoclastic progenitor cell differentiation. This causes an increase in osteoclastic activity via the disinhibition of the osteoblastic paracrine factor. The ultimate result is an increase in extracellular calcium via osteoclastic bone resorption that is due to an increase in osteoclastic cell differentiation.