Roger and his dog, Holly, lived in a house with a big backyard full of old oak trees. One oak tree was very big, twisted and scary looking. It cast a spooky shadow over the ground. One day Roger and Holly were playing in the backyard, then suddenly the scary tree's roots awoke and dragged them into a strange bright portal within its trunk. Roger and Holly fell down a long dark tunnel, terrified of what lay below. At the bottom, Roger discovers the magic of the tree. Holly could now talk. Their journey begins through dark cold caves and endless slimy tunnels with weird creatures waiting for Roger and Holly to enter their territory. Along their way back home, they encounter many misadventures. These misadventures were mainly the result of Roger’s ability to attract trouble and not take Holly's advice. Can Roger and Holly find their way home?

Hyperkalemic periodic paralysis (HEPP) is an inherited, autosomal disorder characterized by myotonia and periodic paralysis in skeletal muscle. The hallmark of the disease is a severe sensitivity to the K+-induced force depression, the cause of the paralysis. Previous studies have provided evidence that the sensitivity to the K+-induced force depression can be alleviated when the Cl- conductance (GCl) is lowered. However, those studies were carried out at non-physiological temperatures (25°-30°C) and few stimulation frequencies. The overarching goal of this study was to examine whether manipulating GCl pharmacologically was a viable target for treating HEPP. This work sought to document the interactive effect of K+ and Cl- on force development in mouse skeletal muscle at 37°C, over a wide range of stimulation frequencies. Secondly, experiments were undertaken to determine if a reduction in GCl could protect against the severe K+ sensitivity in HEPP. The results show that in wildtype muscle, a reduction in GCl improved force generation at high [K+]e at stimulation frequencies that naturally occur in vivo for mouse EDL and soleus. While the effect in wildtype muscles was proof of principle that a reduction in GCl may be a potential approach to treat HEPP patients, the effects of reduced GCl at high [K+]e was quite variable in HEPP muscles. In a few cases, lowering GCl did improve force generation at high [K+]e. However, in most cases the decrease in GCl exacerbated the force depression at high [K+]e, suggesting that more studies will be necessary to understand the variability in the Cl- effect to conclude whether a decrease in GCl is a viable approach to treat HEPP patients.