RYR1 has two sites believed to be important for reacting to changing Ca2+ concentrations: the A-site and the I-site. The A-site is a high affinity Ca2+ binding site that mediates RYR1 opening. The I-site is a lower affinity site that mediates the proteins closing. Caffeine, halothane, and other triggering agents act by drastically increasing the affinity of the A-site for Ca2+ and concomitantly decreasing the affinity of the I-site in mutant proteins. Mg2+ also affect RYR1 activity, causing the protein to close by acting at either the A- or I-sites. In MH mutant proteins, the affinity for Mg2+ at either one of these sites is greatly reduced. The result of these alterations is greatly increased Ca2+ release due to a lowered activation and heightened deactivation threshold. The process of sequestering this excess Ca2+ consumes large amounts of adenosine triphosphate (ATP), the main cellular energy carrier, and generates the excessive heat (hyperthermia) that is the hallmark of the disease. The muscle cell is damaged by the depletion of ATP and possibly the high temperatures, and cellular constituents "leak" into the circulation, including potassium, myoglobin, creatine, phosphate and creatine kinase.The other known causative gene for MH is CACNA1S, which encodes an L-type voltage-gated calcium channel α-subunit. There are two known mutations in this protein, both affecting the same residue, R1086. This residue is located in the large intracellular loop connecting domains 3 and 4, a domain possibly involved in negatively regulating RYR1 activity.
Body resistance
The voltage necessary for electrocution depends on the current through the body and the duration of the current. Ohms law states that the current drawn depends on the resistance of the body. The resistance of human skin varies from person to person and fluctuates between different times of day. The NIOSH states "Under dry conditions, the resistance offered by the human body may be as high as 100,000 ohms. Wet or broken skin may drop the bodys resistance to 1,000 ohms," adding that "high-voltage electrical energy quickly breaks down human skin, reducing the human bodys resistance to 500 ohms".The International Electrotechnical Commission gives the following values for the total body impedance of a hand to hand circuit for dry skin, large contact areas, 50 Hz AC currents (the columns contain the distribution of the impedance in the population percentile; for example at 100 V 50% of the population had an impedance of 1875Ω or less):

Skin
The voltage-current characteristic of human skin is non-linear and depends on many factors such as intensity, duration, history, and frequency of the electrical stimulus. Sweat gland activity, temperature, and individual variation also influence the voltage-current characteristic of skin. In addition to non-linearity, skin impedance exhibits asymmetric and time varying properties. These properties can be modeled with reasonable accuracy. Resistance measurements made at low voltage using a standard ohmmeter do not accurately represent the impedance of human skin over a significant range of conditions. For sinusoidal electrical stimulation less than 10 volts, the skin voltage-current characteristic is quasilinear.