The effect of apamin, a small conductance calcium activated potassium (SK) channel blocker, on a mouse model of neurofibromatosis 1.

Abstract Neurofibromatosis 1 (NF1) is a common genetic disorder known to cause a variety of physiological symptoms such as the formation of both benign and malignant tumors, and is also known to cause visuospatial learning deficits. Mouse models of NF1 show increased GTP activation of ras which may alter K+ channels. One candidate K+ channel that may contribute to deficits in NF1 is the SK (small conductance calcium-activated potassium) channel due to its role in regulation of long term potentiation (LTP), a mechanism of learning which has been shown to be impaired in Nf1 +/− mice. We found that administration of apamin (SK antagonist) either through i.p. injection or micro-osmotic pump to Nf1 +/− mice significantly improved performance on the water maze task in comparison to saline treated Nf1 +/− mice on the third day of training and on the corresponding probe test. In this study we demonstrate a possible mechanism for the learning deficits seen in Nf1 +/− mice and a possible drug therapy for rescuing these deficits.