Publication Date


Document Type


Committee Members

Sherif M. Elbasiouny, Ph.D., P.E. (Advisor); Mary Fendley, Ph.D. (Committee Member); Matt Sherwood, Ph.D. (Committee Member)

Degree Name

Master of Science in Biomedical Engineering (MSBME)


Kv2.1 channels mediate slow-activating K+ rectifier current within the membrane of spinal motoneurons (MNs), and they are known to co-localize with other synapses and ion channels. Although Kv2.1 channels are suggested to regulate MN excitability, little research has gone into investigating its potential contribution to MN-altered excitability in Amyotrophic Lateral Sclerosis (ALS). Using the male SOD1-G93A mouse model of ALS, we examined Kv2.1 cluster area and density in lumbar MNs at four key stages of disease progression. In our experiments, MNs were separated by type via SK3 immunoreactivity in order to isolate and compare the responses of disease-resistant (slow; SK3+) vs. disease-vulnerable (fast; SK3-) MNs at postnatal (P) days P10, P30, P90, and end-stage (ES; P120-140). Our results show that in disease-resistant MNs cluster area does not change relative to wild-type until ES when it significantly decreases. In disease-vulnerable MNs cluster area is increased at P90 before also significantly decreasing at ES. Additionally, no changes were found in cluster density throughout disease progression. Electrophysiological recordings using the whole-cord in-vitro spinal cord preparation supported an increase in cluster area at P90 by demonstrating lower net excitability in SOD MNs relative to wild-type, further suggesting pathologically decreased MN activity. These results provide critical, novel information on how disease-resistant vs. disease-vulnerable MNs regulate their excitability throughout ALS.

Page Count


Department or Program

Department of Biomedical, Industrial & Human Factors Engineering

Year Degree Awarded