Why does lower blood calcium levels (or lower calcium levels in ECF) cause nervous hyperexcitaton? Why does it cause over stimulation of nerves and muscles and spasmic contractions of muscles?
This is why undersecretion of parathormone causes parathyroid tetany.
I am aware of the role of calcium in opening the synaptic vesicles for transmission of impulses and the role of calcium in muscle contraction but fail to understand how that might hep me understand the overexcitation of nerves and spasmic contraction of muscles. It actually seems that higher calcium in ECF might cause over stimulation and spasms of muscles due to sustained contraction.

  • $\begingroup$ I read up on the said article, and yes, it does make sense. I however don't understand how a low ECF value of calcium would cause hyperpolarisation. Technically, for that diffusion to happen, the ECF Ca has to drop below the ICF Ca, which is extremely low. Is there a disproptionate decrease in Ca levels, causing the ECF to drop way below the ICF level? Also let's assume that it's not the membrane permeability to Ca that's causing the stimuli. Would a reduced ECF Ca level cause a decreased threshold level of AP in case of application of an external stimulus? In which case, for tetanus to occur, $\endgroup$ – user33677 Jul 1 '17 at 16:21
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From Uptodate on Clinical Manifestations of Hypocalcemia:

Acute hypocalcemia directly increases peripheral neuromuscular irritability [ 1 ]. As measured electromyographically, tetany consists of repetitive high-frequency discharges after a single stimulus. Hyperexcitability of peripheral neurons is probably the most important pathophysiologic effect of hypocalcemia, but hyperexcitability occurs at all levels of the nervous system, including motor end-plates, the spinal reflexes, and the central nervous system.

Guyton and Hall Textbook of Physiology:

The concentration of calcium ions in the extracellular fluid also has a profound effect on the voltage level at which the sodium channels become activated. When there is a deficit of calcium ions, the sodium channels become activated (opened) by very little increase of the membrane potential from its normal, very negative level. Therefore, the nerve fiber becomes highly excitable, sometimes discharging repetitively without provocation rather than remaining in the resting state. In fact, the calcium ion concentration needs to fall only 50 per cent below normal before spontaneous discharge occurs in some peripheral nerves, often causing muscle “tetany.”This is sometimes lethal because of tetanic contraction of the respiratory muscles.

The probable way in which calcium ions affect the sodium channels is as follows:These ions appear to bind to the exterior surfaces of the sodium channel protein molecule. The positive charges of these calcium ions in turn alter the electrical state of the channel protein itself, in this way altering the voltage level required to open the sodium gate.


It is a question of transmembrane potential. Ca++ being a cation, means that if you decrease the amount of ionized calcium in the extra cellular fluid, it conceptually is nearly equivalent to having a more positively charged intracellular fluid. This in turn means that the cell will be closer to its threshold potential for depolarization, therefore accounting for its hyper excitability.

What you should keep in mind, is that when we say something as: "this cell has a transmembrane potential of -70 mV", we always define it relatively to the extra cellular fluid.

edit: I am leaving this incorrect answer because of the interesting comments below.

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    $\begingroup$ Just read this answer because the question got bumped...this answer is very wrong, and exhibits a common misconception about what sets the membrane potential. Reducing extracellular calcium concentrations, if this had no influences on other channels, would have essentially no change on resting potential, because resting permeability to calcium is very low. Even if there was some permeability to calcium, reducing extracellular calcium concentrations would hyperpolarize, rather than depolarize, because calcium is low in cells. $\endgroup$ – Bryan Krause Dec 28 '16 at 20:22
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    $\begingroup$ I'd say the mechanisms are still under study, though there is good experimental evidence for a couple mechanisms: OneFace's answer suggests one of these, particularly the effects on voltage gated sodium channels. Here is one recent paper that seems to identify one mechanism, and their introduction has several other useful citations. When I have time I will write up a full answer. $\endgroup$ – Bryan Krause Dec 29 '16 at 21:24
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    $\begingroup$ As far as your answer, the Goldman equation is crucial. Permeability to calcium is effectively zero at rest, so we normally ignore calcium, but say for a moment it isn't. Opening a calcium conductance shifts the membrane reversal potential towards the calcium reversal potential, which is typically very depolarized, maybe +100mV. If we reduce extracellular calcium, the calcium reversal potential drops, though you have to reduce it a LOT to see a big effect, since the intracellular concentration is so low. $\endgroup$ – Bryan Krause Dec 29 '16 at 21:33
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    $\begingroup$ Also, no charges have to move to change the equilibrium potential: you could run the sodium/potassium pump all day long and if there is no permeability to sodium or potassium, there is no change in the membrane potential. It isn't meaningful ever to just "add positive charges" - they will always come with some other negative species, it's just that that other negative ion might not matter if there is no permeability. $\endgroup$ – Bryan Krause Dec 29 '16 at 21:36
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    $\begingroup$ You can also play around with this GHK calculator - although only Na+, K+, and Cl- ions are available, changes in external sodium concentration will give you at least the same direction of effect as changes in external calcium concentration, because both are positive ions. $\endgroup$ – Bryan Krause Dec 29 '16 at 21:50

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