Chandelier
Senior Member (Voting Rights)
Authors: Klaus Wirth, Jürgen M. Steinacker
Abstract
Severely ill ME/CFS patients are bedridden and suffer from hypersensitivities against light and noise, severe orthostatic intolerance reducing cerebral blood flow, and skeletal muscle symptoms including loss of force, fatigue, pain, fasciculations and cramps.
Since neurological investigations exclude neuronal causes for myasthenia, we assume a muscular pathomechanism.
In previous papers we considered insufficient activity of the Na+/K+-ATPase as the main cause of mitochondrial damage via high intracellular sodium which reverses the transport mode of the sodium-calcium-exchanger to import calcium causing calcium-overload.
Low Na+/K+-ATPase-activity also causes sarcolemmal depolarization leading to less effective action potential propagation and loss of force.
Depolarization brings membrane potential closer to the firing threshold causing hyperexcitability explaining fasciculations and cramps. These raise sodium influx during excitation to further increase the workload of Na+/K+-ATPase. Thereby, depolarization causes further depolarization.
Higher intracellular sodium favors calcium-overload and mitochondrial damage to lower energy supply of Na+/K+-ATPase and to increase reactive-oxygen species that further inhibit it.
Even at rest, muscle is in a state of depolarization. Depolarization and mitochondrial damage reinforce each other.
Thus, dysfunction of Na+/K+-ATPase as a single mechanism can explain the different skeletal muscle symptoms of the severely ill ME/CFS patient comprising loss of force, fatigue and fasciculations.
Last edited:
