Calcium homeostasis disturbance is seen in -

Ans. is 'a' i.e., Malignant hyperthermiao Malignant hyperthermia is a pharmacogenetic condition caused due to mutation of the "Ryanodine receptor gene".Ryanodine receptor gene controls the level of '"cytosolic calcium" and therefore skeletal muscle contraction.o Ryanodine gene encodes ryanodine receptor found in skeletal muscle (RYRI).The encoded protein functions as calcium release channels in the sarcoplasmic reticulum and also serves to connect the sarcoplasmic reticulum and the transverse tubule (T tubulte), present on the cell membrane.Normally depolarisation of the cell membrane is passed intracellularly to the sarcoplasmic reticulum through the T tubules.In cardiac and skeletal muscle depolarisation of the external membrane triggers a rapid release of stored Ca++ from the sarcoplasmic reticulum which generates muscle contraction.o The release is mediated bv ryanodine receptors.When wave of depolarisation reaches the sarcoplasmic reticulum the ryanodine receptors located on the mambrane of sarcoplasmic reticulum, open up to release the calcium from the sarcoplasmic reticulum.o Mutation in RYRI sene causes it to open more easily and close more slowly in respose to certain drugs. As a result large amounts of calcium ions are released from the sarcoplasmic reticulum within muscle cells.The release of abnormally high amount of calcium from the sarcoplasmic reticidum causes uncotrolled anaerobic and aerobic metabolism and sustained muscle contraction.Muscle contractionThe sustained results in clinical manifestation ofrespiratory> metabolic acidosis, muscle rigidity and hyperthermia.If the process continues unabated, adenosine triphosphate depletion eventually causes widespread muscle fiber hypoxia, cell death, rhabdomyolysis which manifests clinically as hyperkalemia and myoglobinuria and an increase in creatine kinase.o Dantrolene is used in the treatment of malignant hyperthermia because it is thoueht to reduce muscle tone and metabolism bypreventing the on soins release of calcium from sarcoplasmic reticulum.Dantrolene sodium binds to RyRI and causes the closure of the sarcoplasmic reticulum calcium channel, thereby reversing the unihibited flow of calcium.