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If you have more calcium in the cell, wouldn’t more attach to troponin and initiate muscle contraction? Why does hypercalcemia cause muscle weakness instead of spasms?

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    $\begingroup$ Muscle weakness caused by hypercalcemia might come from a decrease in excitability (so that less contractions are initiated) rather than from the contraction mechanism itself. $\endgroup$ – biozic Apr 26 '15 at 12:36
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Hypercalcemia does indeed cause muscle spasm, but as someone else wrote, hypercalcemia indicates the calcium levels in blood and not in the sarcoplasmic reticuli.

One example where you can observe that increased calcium leads to increased contraction is when you take the cardiac glycoside, digoxin. Digoxin inhibits the Na+/K+ ATPase causing an increased concentration of intracellular sodium ions. Indirectly, the increased levels of sodium will disturb the sodium gradient (because of the accumulation of sodium ions inside the cell) and stop the Na+/Ca2+ exchanger. The consequence of the disturbance of the sodium/calcium exchanger will lead to the increased levels of calcium and the increased storage of calcium in the sarcoplasmic reticulum and thus cause positive inotropy of the myocytes.

You can read more about it here: Gheorghiade, Mihai, Kirkwood F. Adams, and Wilson S. Colucci. "Digoxin in the management of cardiovascular disorders." Circulation 109.24 (2004): 2959-2964.

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Lets think about sodium channels for a moment. Empirical studies show that calcium has the ability to transiently block sodium channels (1). So if you have a high amount of calcium floating around, what you're doing is blocking the flux of sodium through the neural membranes. Neurons aren't going to fire if there's little or no flux through these sodium ion channels, so if the neurons decrease in their firing rate, yo end up with muscle weakness.

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