Epilepsy is a neurological disorder characterized by neuronal hyperexcitability. Voltage-gated channels such as sodium and potassium channels are implicated in the pathogenesis of epilepsy. It is expected that the loss-of-function (LOF) and gain-of-function (GOF) mutations of potassium channels result in hyperexcitability and hypoexcitability respectively. However, accumulating evidence indicates that even GOF mutations can result in hyperexcitability and epilepsy. One of the proposed explanations is that these mutations occur in inhibitory neurons,hence disinhibition and hyperexcitability happen. Another explanation is that GOF mutations increase the rate of repolarization phase of action potential and thus higher frequency of action potential is produced. Moreover, hyperpolarization induced by potassium channels can stimulate an inward cationic current that can depolarize the membrane potential. These explanations might explain some of the observations but are not enough to explain all of them because GOF mutations can occur in excitatory neurons and not only in inhibitory neurons. Also, if hyperexcitabilityis always attributed to higher frequency of action potentials due to GOF mutations, then hypoexcitability should be always attributed to lower frequency of action potentials due to LOF mutations, which is not the real case. Additionally, the occurrence of depolarization as a result of hyperpolarization can not guarantee the increase in the hyperexcitability as in the case in which the depolarization occurs without hyperpolarization. Accordingly, we aim to provide another explanation from a perspective of quantum mechanics to cover the diversity of epilepsy that manifests due to these mutations. In the present study, the model of quantum tunneling of potassium ions through the closed gate is used to show that potassium ions can depolarize the membrane potential when the barrier height of the closed gate decreases to a certain value at which the quantum tunneling probability and unitary quantum conductance becomes significant to affect the membrane potential. Moreover, this membrane depolarization occurs because the quantum tunnelingprobability and quantum conductance of extracellular potassium ions are higher than these of intracellular potassium ions. This is attributed to the idea that the kinetic energy of extracellular potassium ions is higher than the kinetic energy of intracellular potassium ions. Therefore, the quantum tunneling model predicts that GOF mutations can yield hyperexcitability and thus epileptic manifestations in the neurons via quantum tunneling. The unique aspect of the present study is that the quantum conductance is calculated using the quantum tunneling delay time , which has not been used before in the previous works. This provides further evidence and consistency to the quantum tunneling model of ions

quantum tunneling ; quantum biology; quantum medicine, quantum conductance; epilepsy; potassium channel