Additional Funding Sources
The project described was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under Grant No. P20GM103408.
Abstract
Hypokalemic periodic paralysis is a disease that affects the functioning of the skeletal muscles in the extremities of the body and causes episodes of paralysis due to low serum potassium levels. The research characterized how a mutation in the S4 segment of the third protein domain of sodium voltage-gated ion channels, hNaV1.4, affects skeletal muscles. The mutation, K1126I, where a lysine is substituted for by isoleucine, was detected in a clinical patient with hypokalemic periodic paralysis. The S4 segments of the four protein domains are essential for the skeletal muscles to be able to effectively create and undergo action potentials that occur in skeletal muscles. Data was collected by injecting RNA for wildtype and mutant channels into Xenopus laevis oocytes. Experimentation was done using an electrophysiology technique known as Cut-Open Voltage Clamping. Wildtype and mutant channels were also compared to experiments where inactivation was prohibited. The IFM-QQQ sequence in the RNA hinders inactivation from occurring in the sodium voltage-gated ion channels and allows researchers to understand if the mutation, K1126I, affects the activation of the channels. The electrophysiology technique previously mentioned produced data from the injected oocytes that was then analyzed and compared to understand how the K1126I mutation affected the activities of the S4 segment in the third domain. The current hypothesis is the mutation would decrease activation and increased inactivation which would explain the muscle fibers’ hypo excitability.
Exploration of Hypokalemic Periodic Paralysis Mutation in Sodium Voltage-Gated Ion Channels
Hypokalemic periodic paralysis is a disease that affects the functioning of the skeletal muscles in the extremities of the body and causes episodes of paralysis due to low serum potassium levels. The research characterized how a mutation in the S4 segment of the third protein domain of sodium voltage-gated ion channels, hNaV1.4, affects skeletal muscles. The mutation, K1126I, where a lysine is substituted for by isoleucine, was detected in a clinical patient with hypokalemic periodic paralysis. The S4 segments of the four protein domains are essential for the skeletal muscles to be able to effectively create and undergo action potentials that occur in skeletal muscles. Data was collected by injecting RNA for wildtype and mutant channels into Xenopus laevis oocytes. Experimentation was done using an electrophysiology technique known as Cut-Open Voltage Clamping. Wildtype and mutant channels were also compared to experiments where inactivation was prohibited. The IFM-QQQ sequence in the RNA hinders inactivation from occurring in the sodium voltage-gated ion channels and allows researchers to understand if the mutation, K1126I, affects the activation of the channels. The electrophysiology technique previously mentioned produced data from the injected oocytes that was then analyzed and compared to understand how the K1126I mutation affected the activities of the S4 segment in the third domain. The current hypothesis is the mutation would decrease activation and increased inactivation which would explain the muscle fibers’ hypo excitability.