A POSSIBLE ROLE FOR INOSITOL 1,4,5-TRISPHOSPHATE (IP3) IN MALIGNANT HYPERTHERMIA

In Malignant Hyperthermia an increased open probability of the ryanodi ne Ca2+-channels in the SR-membrane primes a higher cytosolic Ca2+-con centration. This in turn accelerates ATP-hydrolysis culminating in a g radual decrease in ATP-levels. At low ATP-levels, IP3-synthesis is bei ng stimulated and the ability of IP3 to release Ca is enhanced. This r esults through the opening of IP3-dependent channels. Ca2+-release thr ough the ryanodine channels and the IP3-dependent channels summate to increase the cytosol Ca2+-levels to such a high value that ATP is hydr olysed below a critical value causing rigor (contracture) of skeletal muscle. Since Ca2+-uptake by the SR is ATP-dependent, Ca2+-uptake will eventually also slow down and so contributes to the rise in cytosol C a2+-concentration.