About 50 different genetic mutations have been identified in association with the periodic paralyses. Each of these mutations affect the structure or function of either a sodium, calcium or potassium ion channel. These mutated ion channels are located in the skeletal muscle membrane. The muscle membrane is an active, living tissue which wraps around the entire surface of each muscle cell. This membrane has an outer surface and an inner surface.
Ion channels are formed of groups of flexible coiled tubes. These create and surround an opening (or pore) which extends from the outside surface of the membrane to its inside surface. The coils open and close the pore by changing its shape. When the sensor on the ion channel receives the proper signal the coiled tubes react. They change the shape of the opening, allowing ions of potassium, calcium or sodium to pass through. The channel remains open only for a fraction of a second, ions flow through, the tube closes and ion flow stops. The ion channel then goes into a “resting” phase, relaxed but ready to respond to a new signal.
The symptoms of PP are caused by fluctuations of serum K+ which primarily affect muscle tone, but a potassium imbalance in either direction also affects other functions in the body, as potassium and sodium are the two ions that “fire up” the electrical grid that our cells operate on.
The muscle cell works best when the membrane is maintained at a certain level of electrical resistance. This resistance is “set” or maintained by the ratio of potassium and salt on either side of the muscle membrane, a ratio controlled by the ion channels. When an ion channel is defective, as in PP, it affects the resistance of the muscle fibre. The resistance of the membrane goes up, making it more difficult to overcome. As membrane resistance rises the muscle becomes less responsive to stimulation, thus weaker. When resistance gets so high that the muscle quits responding at all the result is paralysis.
You might visualize this increased membrane resistance as a dimmer switch controlling a light with an infinite number of settings. It will handle a 100-watt bulb, but let’s say we only had a 50-watt bulb in the drawer, so we stuck that in the socket. When the mark is straight up potassium is at a normal level. When you turn the dial down (dim the lights) you are actually increasing the resistance to the flow of electrons in the wire. That’s just what happens when the level of potassium drops in the blood serum. Cell membranes all over the body become more resistant to stimulation. The muscles get weaker, because nerve stimulation can’t overcome the increased resistance.
If you turn the dial UP the light gets brighter because electrons flow more easily, and resistance to stimulation is reduced. It’s the same in the body. Too much potassium in the blood causes the ion gates to become too sensitive to stimulation. They respond too vigorously, or too often, and they may fire repeatedly until they become stuck in a half-closed position, allowing sodium ions to pour through the membrane into the muscle tissue. This would be like turning the dimmer dial too high, so high that the light bulb pops. In HyperKPP this is the point where weakness becomes paralysis. The muscle packs up and says, “No more movement until you get this wiring problem worked out!”
In PP it’s not the absolute value of potassium in the blood that determines a person’s weakness, it’s the ratio of potassium and sodium inside and outside the muscle cell. The weakness hasn’t anything to do with nerves or nerve signals. The nerve signals arrive and are received, it’s the response (or the lack thereof) which causes the weakness.
Excerpted from: Do I Have Periodic Paralysis? Pursuing a Diagnosis: A Guide for Patients. Copyright © 2007-2020 by Deborah Cavel-Greant. Last reviewed and updated September 10, 2020 Unmodified copies of this booklet may be shared for non-commercial use. Read the license at: https://creativecommons.org/licenses/by-nc-nd/3.0/ for details.